Genomes and Genes
sodium channel blockers
Summary: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Publications261 found, 100 shown here
- International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channelsWilliam A Catterall
Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280
Pharmacol Rev 57:397-409. 2005..This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties...
- Voltage-gated sodium channels and pain pathwaysJohn N Wood
Molecular Nociception Group, Department of Biology, University College, Gower Street, London WC1E 6BT, UK
J Neurobiol 61:55-71. 2004Acute, inflammatory, and neuropathic pain can all be attenuated or abolished by local treatment with sodium channel blockers such as lidocaine...
- Action potential generation requires a high sodium channel density in the axon initial segmentMaarten H P Kole
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia
Nat Neurosci 11:178-86. 2008..In conclusion, action potential generation requires a high Na(+) channel density at the AIS, which is maintained by tight anchoring to the actin cytoskeleton...
- Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disordersMassimo Mantegazza
Dipartimento di Neurofisiopatologia, Fondazione Istituto Neurologico C Besta, Milano, Italy
Lancet Neurol 9:413-24. 2010....
- Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockersAlexander M Binshtok
Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
Nature 449:607-10. 2007....
- The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4M F Sheets
The Nora Eccles Harrison Cardiovascular Research and Training Institute and Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84112, USA
Biophys J 77:747-57. 1999....
- The tetrodotoxin binding site is within the outer vestibule of the sodium channelHarry A Fozzard
Department of Medicine, University of Chicago Hospitals, Chicago, IL 60637, USA
Mar Drugs 8:219-34. 2010..One site in the channel's domain I P loop determines affinity differences in mammalian isoforms...
- muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficitsJ Ekberg
Institute for Molecular Bioscience and School of Biomedical Sciences, University of Queensland, QLD 4072, Australia
Proc Natl Acad Sci U S A 103:17030-5. 2006..The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na(v)1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists...
- Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the ratShuangsong Hong
Department of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
J Biol Chem 279:29341-50. 2004..These results suggest that both TTX-S and TTX-R sodium channels play important roles and that differential phosphorylation of sodium channels involving both serine/threonine and tyrosine sites contributes to painful diabetic neuropathy...
- Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSPV Monica Bricelj
Institute for Marine Biosciences, National Research Council, Halifax, Nova Scotia B3H 3Z1, Canada
Nature 434:763-7. 2005..Furthermore, global expansion of PSP to previously unaffected coastal areas might result in long-term changes to communities and ecosystems...
- Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent blockJean Francois Desaphy
Division of Pharmacology, Department of Pharmaco Biology, University of Bari, Bari I 70125, Italy
J Physiol 554:321-34. 2004..This study offers a pharmacogenetic strategy to better address treatment in individual myotonic patients...
- Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous late Na(+) current in the heartLin Wu
Pharmacological Sciences, Gilead Sciences, Palo Alto, California 94304, USA
Am J Physiol Heart Circ Physiol 297:H1048-57. 2009..Inhibition of this current partially reverses MAPD prolongation and abolishes arrhythmic activity caused by I(K) inhibitors...
- Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazineAlexander Burashnikov
Masonic Medical Research Laboratory, Utica, NY 13501, USA
Circulation 116:1449-57. 2007..The development of selective atrial antiarrhythmic agents is a current strategy for suppression of atrial fibrillation (AF)...
- Late sodium current contributes to diastolic cell Ca2+ accumulation in chronic heart failureNidas A Undrovinas
Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202 2689, USA
J Physiol Sci 60:245-57. 2010..We conclude that INaL contributes to diastolic Ca2+ accumulation and spontaneous Ca2+ release in HF...
- Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8Josephine Lai
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
Pain 95:143-52. 2002..These data provide direct evidence linking NaV1.8 to neuropathic pain. As NaV1.8 expression is restricted to sensory neurons, this channel offers a highly specific and effective molecular target for the treatment of neuropathic pain...
- Presynaptic Na+ channels: locus, development, and recovery from inactivation at a high-fidelity synapseRicardo M Leão
The Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
J Neurosci 25:3724-38. 2005..We propose that the high density and polarized locus of Na+ channels on a long heminode are critical design features that allow the mature calyx of Held terminal to fire reliably at frequencies near 1 kHz...
- Subcellular heterogeneity of sodium current properties in adult cardiac ventricular myocytesXianming Lin
Leon H Charney Division of Cardiology, New York University School of Medicine, New York, New York 10016, USA
Heart Rhythm 8:1923-30. 2011..Sodium channel α-subunits in ventricular myocytes (VMs) segregate either to the intercalated disc or to lateral membranes, where they associate with region-specific molecules...
- Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers: insights from mathematical models and experimental correlatesPhilippe Comtois
Department of Medicine and Research Center, Montreal Heart Institute and Universite de Montreal, Montreal, Canada
Am J Physiol Heart Circ Physiol 295:H1489-504. 2008..These results provide new insights into the mechanisms by which rapidly unbinding class I antiarrhythmic agents, a class including several novel compounds of considerable promise, terminate AF...
- A novel conotoxin from Conus striatus, mu-SIIIA, selectively blocking rat tetrodotoxin-resistant sodium channelsCheng Zhong Wang
Key Laboratory of Proteomics, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Toxicon 47:122-32. 2006....
- On the relationship between block of the cardiac Na⁺ channel and drug-induced prolongation of the QRS complexA R Harmer
Safety Assessment UK, AstraZeneca R and D Alderley Park, Macclesfield, UK
Br J Pharmacol 164:260-73. 2011..However, interpretation of hNa(v) 1.5 blocking potency requires knowledge of how hNa(v) 1.5 block translates into prolongation of the QRS complex...
- Early blockade of injured primary sensory afferents reduces glial cell activation in two rat neuropathic pain modelsW Xie
Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267 0531, USA
Neuroscience 160:847-57. 2009..We tested effects of locally inhibiting sensory neuron activity with sodium channel blockers on satellite glial cell activation in a rat spinal nerve ligation (SNL) model...
- Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogramDeb Kumar Mojumder
College of Optometry, University of Houston, 505 J Davis Armistead Bldg, 4901 Calhoun Road, Houston, TX 77204 2020, USA
J Physiol 586:2551-80. 2008..These findings indicate that activation of Na(v) channels in ON cone bipolar cells affects the b-wave of the rat ERG and must be considered when analysing results of ERG studies of retinal function...
- Voltage-gated Sodium Channel Activity Promotes Cysteine Cathepsin-dependent Invasiveness and Colony Growth of Human Cancer CellsLudovic Gillet
INSERM U921, Nutrition, Croissance et Cancer, and INSERM U618, Protéases et Vectorisation Pulmonaires, Universite Francois Rabelais, FacultédeMédecine, 37032 Tours, France
J Biol Chem 284:8680-91. 2009..This general mechanism could lead to the identification of new targets allowing the therapeutic prevention of metastases...
- Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channelsStephan A Pless
Department of Anesthesiology, University of British Columbia, 2350 Health Science Mall, Vancouver, British Columbia, V6T 1Z3 Canada
Nat Commun 2:351. 2011..Our data shed new light on drug-target interactions underlying the inhibition of cardiac sodium channels by clinically relevant drugs and provide information for the directed design of AADs...
- Scorpion toxins specific for Na+-channelsL D Possani
Department of Molecular Recognition and Structural Biology, Institute of Biotechnology, National Autonomous University of Mexico, Avenida Universidad 2001, Cuernavaca, Mexico
Eur J Biochem 264:287-300. 1999..The presence of an intron at the DNA level, situated in the middle of the signal peptide, has been demonstrated...
- Nonequilibrium calcium dynamics regulate the autonomous firing pattern of rat striatal cholinergic interneuronsJoshua A Goldberg
Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, USA
J Neurosci 29:8396-407. 2009..During irregular firing, calcium entry at both timescales can be detected, suggesting that an interaction between the medium and slow calcium-dependent afterhyperpolarizations may underlie this firing pattern...
- GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory neuronesMark D Baker
Molecular Nociception Group, Department of Biology, Medawar Building, University College London, Gower Street, UK
J Physiol 548:373-82. 2003..These findings suggest that regulation of the persistent current has important consequences for nociceptor excitability...
- Electrostatic contributions of aromatic residues in the local anesthetic receptor of voltage-gated sodium channelsChristopher A Ahern
Department of Molecular Physiology and Biophysics, Institute of Hyperexcitability, Jefferson Medical College, Philadelphia, PA, USA
Circ Res 102:86-94. 2008..These results fine tune our understanding of local anesthetic inhibition of voltage-gated sodium channels and will help the design of safer and more salutary therapeutic agents...
- A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugsCarmen R Valdivia
Department of Medicine and Physiology, University of Wisconsin, Madison, WI, USA
Cardiovasc Res 62:53-62. 2004..Mutations in SCN5A cause arrhythmia syndromes including Brugada syndrome (BrS) and congenital long QT syndrome subtype 3 (LQT3). Here, we report a trafficking defective BrS-causing SCN5A mutation that was drug-rescued...
- Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancerDaniel Diaz
Departamento de Biofisica, Instituto de Fisiologia Celular, Universidad Nacional Autónoma de México México, DF, Mexico
J Cell Physiol 210:469-78. 2007..The results show for the first time the functional expression of VGSC in primary cultures from human CaC, and suggest that these channels might be considered as potential molecular markers for this type of cancer...
- Alpha-scorpion toxin impairs a conformational change that leads to fast inactivation of muscle sodium channelsFabiana V Campos
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA
J Gen Physiol 132:251-63. 2008..These results are consistent with the proposed model, in which Ts3 specifically impairs the fraction of the movement of the S4-DIV that allows fast inactivation to occur at normal rates...
- SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypesCaroline R Fertleman
Department of Paediatrics and Child Health, Royal Free and University College Medical School, University College London, 5 University Street, London WC1E 6JJ, United Kingdom
Neuron 52:767-74. 2006..PEPD and PE are allelic variants with distinct underlying biophysical mechanisms and represent a separate class of peripheral neuronal sodium channelopathy...
- Ranolazine selectively blocks persistent current evoked by epilepsy-associated Naν1.1 mutationsKristopher M Kahlig
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232 0275, USA
Br J Pharmacol 161:1414-26. 2010..Here, we investigated the ability of ranolazine to preferentially inhibit increased persistent current evoked by mutant Na(V) 1.1 channels...
- Voltage-gated sodium channel blockers; target validation and therapeutic potentialJohn N Wood
Molecular Nociception Group, Biology UCL, Gower Street, London WC1 E 6BT
Curr Top Med Chem 5:529-37. 2005..They underlie electrical signalling in nerve and muscle. It has long been known that sodium channel blockers are anaesthetics as well as powerful analgesics when delivered at low concentrations...
- Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motilityS P Fraser
Imperial College of Science, Technology, and Medicine, Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College Road, London, United Kingdom
J Cell Physiol 195:479-87. 2003..The results, taken together, would suggest strongly that functional VGSC expression enhances cellular motility of PCa cells. The relevance of these findings to the metastatic process in PCa is discussed...
- Two types of cone bipolar cells express voltage-gated Na+ channels in the rat retinaJinjuan Cui
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
Vis Neurosci 25:635-45. 2008..Multiple spike-like potentials were also observed in some of these cells. Results of this study provide valuable insights into the function of voltage-gated Na+ channels of retinal bipolar cells in retinal processing...
- Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic painTemugin Berta
Department of Anesthesiology, University Hospital Center and University of Lausanne, CH 1011 Lausanne, Switzerland
Mol Cell Neurosci 37:196-208. 2008..Our results describe altered neuronal electrogenesis following SNI that is likely induced by a complex regulation of VGSCs...
- Electrostatic and steric contributions to block of the skeletal muscle sodium channel by mu-conotoxinKwokyin Hui
Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
J Gen Physiol 119:45-54. 2002....
- Ion channels associated with the ectopic discharges generated after segmental spinal nerve injury in the ratX Liu
Marine Biomedical Institute, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA
Brain Res 900:119-27. 2001....
- Voltage-gated Na+ channels: multiplicity of expression, plasticity, functional implications and pathophysiological aspectsJ K J Diss
Neuroscience Solutions to Cancer Research Group, Department of Biological Sciences, Imperial College London, South Kensington Campus, Imperial College Road, London, SW7 2AZ, UK
Eur Biophys J 33:180-93. 2004....
- A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes to neuronal hyperexcitability and displays reduced lidocaine sensitivityPatrick L Sheets
Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, 950 West Walnut St, R2 468, Indianapolis, IN 46202, USA
J Physiol 581:1019-31. 2007..7 and suggests that the response of individuals with hereditary erythromelalgia to lidocaine treatment may be determined, at least in part, by their specific genotype...
- Targeting of sodium channel blockers into nociceptors to produce long-duration analgesia: a systematic study and reviewD P Roberson
FM Kirby Neurobiology Center and Department of Neurology, Children s Hospital, Boston, MA 02115, USA
Br J Pharmacol 164:48-58. 2011..This involves co-administration of QX-314 and a TRPV1 agonist to produce a long-lasting local analgesia. For potential clinical use we propose using lidocaine as the TRPV1 agonist, because it activates TRPV1 at clinical doses...
- RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agentsPeter M R Orth
Cardiome Pharma Corporation, 6th Floor, Vancouver BC, Canada
Cardiovasc Res 70:486-96. 2006..Further, RSD1235's ability to reverse the pro-arrhythmic actions of the class III agents dofetilide and clofilium was assessed in isolated Purkinje fibers and an in vivo model of torsades de pointes (TdP)...
- Zonisamide versus topiramate in migraine prophylaxis: a double-blind randomized clinical trialSeyed Ehsan Mohammadianinejad
Department of Neurology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Clin Neuropharmacol 34:174-7. 2011....
- The relationship between sodium channel inhibition and anticonvulsant activity in a model of generalised seizure in the ratCharles H Large
epartment of Molecular and Cellular Biology, Neuroscience Centre of Excellence for Drug Discovery, Medicines Research Centre, GlaxoSmithKline S p A, Via Fleming 4, Verona 37135, Italy
Epilepsy Res 85:96-106. 2009..We found that a higher unbound concentration of the drug in the brain was required for anticonvulsant efficacy than would be expected given its sodium channel blocking potency...
- Na(v)1.5 sodium channels in a human microglial cell lineE Nicholson
MRC Centre for Synaptic Plasticity, University of Bristol, School of Medical Sciences, Bristol, BS8 1TD, UK
J Neuroimmunol 215:25-30. 2009..The presence of the Na(V)1.5 subunit in microglial cells is discussed with respect to its reported roles in phagocytosis, proliferation and migration of other non-cardiac cells...
- The pharmacological response of ischemia-related atrial fibrillation in dogs: evidence for substrate-specific efficacyLena Rivard
Research Center and Department of Medicine, Montreal Heart Institute, Universite de Montreal, Montreal, Canada
Cardiovasc Res 74:104-13. 2007..The present study assessed the effects of class 1-4 antiarrhythmic-drugs on the electrophysiological consequences of acute atrial ischemia, and compared effects in ischemic AF with those in vagal AF...
- Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in ratsY Zhang
Department of Anesthesiology, Fuwai Hospital and Cardiovascular Institute, Beijing, China
Br J Pharmacol 159:872-8. 2010....
- Molecular design of new sodium channel blockersPing Li
Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China
Biochem Biophys Res Commun 414:321-5. 2011..This work will enhance our understanding of the molecular determinants of toxins affecting VGSCs and aid the rational design of subtype-specific blockers of the channels...
- Sodium current in human intestinal interstitial cells of CajalPeter R Strege
Enteric Neuroscience Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA
Am J Physiol Gastrointest Liver Physiol 285:G1111-21. 2003..A mechanosensitive Na+ channel current is present in human intestinal ICC and appears to play a role in the control of intestinal motor function...
- A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in neuropathic ratsSteve McGaraughty
Neuroscience Research, Abbott Laboratories, R4PM, AP9 1, 100 Abbott Park Rd, Abbott Park, IL 60064 6118, USA
J Pharmacol Exp Ther 324:1204-11. 2008..However, Na(v)1.8 sodium channels on central terminals seem to be key to the modulation of spontaneous firing in SNL rats...
- Acid solution is a suitable medium for introducing QX-314 into nociceptors through TRPV1 channels to produce sensory-specific analgesic effectsHe Liu
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China
PLoS ONE 6:e29395. 2011....
- Trafficking defects and gating abnormalities of a novel SCN5A mutation question gene-specific therapy in long QT syndrome type 3Yanfei Ruan
Cardiovascular Genetics Program, Leon H Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA
Circ Res 106:1374-83. 2010b>Sodium channel blockers are used as gene-specific treatments in long-QT syndrome type 3, which is caused by mutations in the sodium channel gene (SCN5A). Response to treatment is influenced by biophysical properties of mutations.
- Mechanisms of atrial-selective block of Na⁺ channels by ranolazine: I. Experimental analysis of the use-dependent blockAndrew C Zygmunt
Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501, USA
Am J Physiol Heart Circ Physiol 301:H1606-14. 2011....
- Block of wild-type and inactivation-deficient cardiac sodium channels IFM/QQQ stably expressed in mammalian cellsA O Grant
Departments of Medicine and Pediatrics, Duke University, Durham, NC 27706, USA
Biophys J 79:3019-35. 2000..The qualitative differences in use-dependent block appear to be the result of differences in drug dissociation rate. The inactivation gate may play a trapping role during exposure to some sodium channel blocking drugs...
- Effects of pre-emptive drug treatment on astrocyte activation in the cuneate nucleus following rat median nerve injuryJiann Jy Chen
Department of Medical Research, Tao Yuan General Hospital, Taoyuan, Taiwan
Pain 148:158-66. 2010..In conclusion, suppressing reactions to injury, such as the generation of ectopic discharges and activation of NMDA receptors, can decrease astrocyte activation in the CN and attenuate neuropathic pain sensations...
- Sodium channel molecular conformations and antiarrhythmic drug affinityMichael F Sheets
University of Utah, The Nora Eccles Harrison Cardiovascular Research and Teaching Institute, Department of Internal Medicine, Salt Lake City, UT 84112, USA
Trends Cardiovasc Med 20:16-21. 2010....
- Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockersEliseu O De Oliveira
Drug Discovery Program, Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA
Bioorg Med Chem 19:4322-9. 2011..We also present a potential binding mode for (S)-hermitamide B in the BTX-binding site and electrophysiology showing that these compounds are potent blockers of the hNav1.2 voltage-gated sodium channel...
- Point mutations at N434 in D1-S6 of mu1 Na(+) channels modulate binding affinity and stereoselectivity of local anesthetic enantiomersC Nau
Department of Anesthesia Research Laboratories, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Mol Pharmacol 56:404-13. 1999..We propose that in inactivated channels, residue mu1-N434 interacts directly with the positively charged moiety of LAs and that D1-S6 and D4-S6 form a domain-interface site for binding of BTX and LAs in close proximity...
- Effects of a new potent analog of tocainide on hNav1.7 sodium channels and in vivo neuropathic pain modelsC Ghelardini
Department of Preclinical and Clinical Pharmacology, Faculty of Pharmacy, University of Florence, Florence, Italy
Neuroscience 169:863-73. 2010..Overall, these results indicate NeP1 as a new promising lead compound for further development in the treatment of chronic pain of neuropathic origin...
- Block of Na+ currents and suppression of action potentials in embryonic rat dorsal root ganglion neurons by ranolazineRyoko Hirakawa
Department of Biology, Gilead Sciences Inc, 1651 Page Mill Road, Palo Alto, CA 94304, USA
Neuropharmacology 62:2251-60. 2012....
- Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental areaChunyu Deng
Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103 2714, USA
Neuropsychopharmacology 34:1233-44. 2009..Furthermore, ethanol stimulation of a single dopaminergic neuron is capable of eliciting the release of somatodendritic dopamine, which is sufficient to influence glutamatergic transmission at individual synapses...
- Substituted biaryl pyrazoles as sodium channel blockersSriram Tyagarajan
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
Bioorg Med Chem Lett 20:5480-3. 2010..A series of low molecular weight biaryl substituted pyrazole carboxamides were identified with good in-vitro potency and in-vivo efficacy. Compound 26, a Nav1.7 blocker has excellent efficacy in the Chung model of neuropathic pain...
- Animal peptides targeting voltage-activated sodium channelsBert Billen
Laboratory of Toxicology, KULeuven, Campus Gasthuisberg O and N 2, PO Box 922, Herestraat 49, 3000 Leuven, Belgium
Curr Pharm Des 14:2492-502. 2008..This review puts venom peptides from spiders, scorpions and cone snails that target voltage-activated sodium channels in the spotlight, and addresses their potential therapeutical applications...
- Glucose stimulates glucagon release in single rat alpha-cells by mechanisms that mirror the stimulus-secretion coupling in beta-cellsHervør Lykke Olsen
Lilly Research Laboratories, Essener Bogen 7, D 22419 Hamburg, Germany
Endocrinology 146:4861-70. 2005..The stimulatory action of glucose in isolated alpha-cells contrasts with the suppressive effect of the sugar in intact islets and highlights the primary importance of islet paracrine signaling in the regulation of glucagon release...
- A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the ratMichael F Jarvis
Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064, USA
Proc Natl Acad Sci U S A 104:8520-5. 2007..These data demonstrate that acute and selective pharmacological blockade of Na(v)1.8 sodium channels in vivo produces significant antinociception in animal models of neuropathic and inflammatory pain...
- Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channelsMin Min Zhang
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA
J Biol Chem 282:30699-706. 2007..need exists for the discovery and development of novel non-opioid analgesics, such as subtype-selective sodium channel blockers. Micro-conotoxin KIIIA is representative of micro-conopeptides previously characterized as inhibitors of ..
- Effects of tetrodotoxin on the mammalian cardiovascular systemThomas Zimmer
Institute of Physiology II, Friedrich Schiller University, Kollegiengasse 9, 07743 Jena, Germany
Mar Drugs 8:741-62. 2010..Altogether, these data strongly suggest that TTX sensitive Na+ channels, detected more recently in various heart tissues, are not involved in excitation phenomena in the healthy adult heart of higher mammals...
- Sodium channel activity modulates multiple functions in microgliaJoel A Black
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale School of Medicine, New Haven, Connecticut 06518, USA
Glia 57:1072-81. 2009..6) indicate that Nav1.6 plays a role in microglial migration. The results demonstrate that the activity of sodium channels contributes to effector roles of activated microglia...
- Inhibition of tetrodotoxin (TTX)-resistant and TTX-sensitive neuronal Na(+) channels by the secretolytic ambroxolThomas Weiser
Department CNS Research, Boehringer Ingelheim Pharma KG, Ingelheim, Germany
Mol Pharmacol 62:433-8. 2002..g., lidocaine or benzocaine), the potency for Na(+) channel block was relatively high. A recent clinical trial has further confirmed that ambroxol relieved pain and was beneficial in patients who suffered from sore throat...
- Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxinChong Hyun Lee
School of Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
Channels (Austin) 2:407-12. 2008..We here review the properties of sodium channels and their interaction with TTX, and look at some special examples of TTX resistant channels wherein the benefit of toxin resistance may be offset by other behavioral costs...
- Nociceptors are interleukin-1beta sensorsAlexander M Binshtok
Neural Plasticity Research Group, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Neurosci 28:14062-73. 2008..By acting as an IL-1beta sensor, nociceptors can directly signal the presence of ongoing tissue inflammation...
- Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneuronesG B Miles
Department of Anatomy and Neurobiology, Dalhousie University, Halifax, NS, Canada
J Physiol 566:519-32. 2005..The removal of slow inactivation from this model was sufficient to remove SFA. These data indicate that slow inactivation of the fast, inactivating Na+ conductance is likely to be the key mechanism underlying early SFA in spinal MNs...
- Late sodium current is a new therapeutic target to improve contractility and rhythm in failing heartAlbertas Undrovinas
Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202 2689, USA
Cardiovasc Hematol Agents Med Chem 6:348-59. 2008..g. Ca(2+)- or cytoskeleton- dependent) mechanisms of I(NaL) function...
- Comparative neuroprotective effect of sodium channel blockers after experimental spinal cord injuryOzkan Ates
Inonu University, School of Medicine, Department of Neurosurgery, Turgut Ozal Medical Center, 44069 Malatya, Turkey
J Clin Neurosci 14:658-65. 2007..Previous studies have shown that some voltage-sensitive sodium channel blockers provide powerful neuroprotection...
- Two tarantula peptides inhibit activation of multiple sodium channelsRichard E Middleton
Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey, USA
Biochemistry 41:14734-47. 2002..1 channels with 10-fold less potency than its potency on Na(V) channels. These peptides represent novel tools for exploring the gating mechanisms of several Na(V) and Ca(V) channels...
- Voltage-gated sodium channels in neurological disordersMohamed Chahine
Le Centre de recherches Université Laval Robert Griffard, Quebec City, Guebec, Canada
CNS Neurol Disord Drug Targets 7:144-58. 2008..This review describes the biochemical, biophysical and pharmacological properties of neuronal voltage-gated sodium channels (VGSC) and their implication in several neurological disorders...
- Lidocaine suppresses subthreshold oscillations by inhibiting persistent Na(+) current in injured dorsal root ganglion neuronsH Dong
Institute of Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi an, Shaanxi, China
Physiol Res 57:639-45. 2008..Low concentration of lidocaine (10 micromol/l) suppresses SMPO by selectively inhibiting I(NaP), but not I(NaT), in chronically compressed DRG neurons...
- The role of sodium channels in neuropathic painMarc Rogers
Xention Ltd, Iconix Park, Pampisford, Cambridge CB2 4EF, United Kingdom
Semin Cell Dev Biol 17:571-81. 2006..One of the future challenges in the development of novel sodium channel blockers is to design and synthesise isoform-selective channel inhibitors...
- Chinese-scorpion (Buthus martensi Karsch) toxin BmK alphaIV, a novel modulator of sodium channels: from genomic organization to functional analysisZhi fang Chai
Graduate School of the Chinese Academy of Sciences, Shanghai Institute of Physiology, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People s Republic of China
Biochem J 399:445-53. 2006....
- Proximal persistent Na+ channels drive spike afterdepolarizations and associated bursting in adult CA1 pyramidal cellsCuiyong Yue
Department of Physiology, Institute of Medical Sciences, Hebrew University Hadassah Faculty of Medicine, Jerusalem 91120, Israel
J Neurosci 25:9704-20. 2005..Through this action, proximal INaP critically determines the firing mode and spike output of adult CA1 pyramidal cells...
- Voltage-gated sodium channels: therapeutic targets for painSulayman D Dib-Hajj
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06520 8018, USA
Pain Med 10:1260-9. 2009..To provide an overview of the role of voltage-gated sodium channels in pathophysiology of acquired and inherited pain states, and of recent developments that validate these channels as therapeutic targets for treating chronic pain...
- Exploring the obscure profiles of pharmacological binding sites on voltage-gated sodium channels by BmK neurotoxinsZhi Rui Liu
Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, China
Protein Cell 2:437-44. 2011....
- Voltage-gated sodium channels and hyperalgesiaJosephine Lai
Departments of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
Annu Rev Pharmacol Toxicol 44:371-97. 2004..Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain...
- Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosisMassimo Pieri
Department of Neuroscience, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Exp Neurol 215:368-79. 2009....
- Sodium channels in transient retinal bipolar cells enhance visual responses in ganglion cellsTomomi Ichinose
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Neurosci 25:1856-65. 2005..Our results suggest that bipolar cell sodium channels augment transient signals and contribute to the temporal segregation of visual information...
- Coordinated changes in dendritic arborization and synaptic strength during neural circuit developmentYi Rong Peng
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Neuron 61:71-84. 2009....
- Cooccupancy of the outer vestibule of voltage-gated sodium channels by micro-conotoxin KIIIA and saxitoxin or tetrodotoxinMin Min Zhang
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA
J Neurophysiol 104:88-97. 2010..The demonstration that two interacting ligands ("syntoxins") occupy adjacent sites raises the possibility of evolving a much more sophisticated neuropharmacology of VGSCs...
- The discovery and characterization of a proton-gated sodium current in rat retinal ganglion cellsSarah Lilley
Neural Injury and Repair Group, Centre for Neuroscience Research, King s College London, Guy s Campus, London, SE1 1UL, United Kingdom
J Neurosci 24:1013-22. 2004..The presence of a proton-gated current in the neural retina suggests that ASICs may have a more diverse role in the CNS...
- μ-conotoxin KIIIA derivatives with divergent affinities versus efficacies in blocking voltage-gated sodium channelsMin Min Zhang
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA
Biochemistry 49:4804-12. 2010....
- Navβ subunits modulate the inhibition of Nav1.8 by the analgesic gating modifier μO-conotoxin MrVIBMichael J Wilson
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA
J Pharmacol Exp Ther 338:687-93. 2011..Our results raise the possibility that μO-conotoxins and perhaps other gating modifiers may provide a means to functionally assess the β-subunit composition of VGSC complexes in neurons...
- Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminalsWei Ouyang
Department of Anesthesiology, Box 50, LC 203, 525 E 68th St, Weill Medical College of Cornell University, New York, NY 10021, USA
Mol Pharmacol 64:373-81. 2003..Inhibition of voltage-gated Na+ channels may contribute to the presynaptic effects of general anesthetics on nerve terminal excitability and neurotransmitter release...
- Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5AShao Wu Ou
Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8 35 1 Sakuragaoka, Kagoshima 890 8544, Japan
Eur J Neurosci 22:793-801. 2005..The IC50 for the TTX block was approximately 8 microM in both variants. These results suggest that SCN5A has a newly identified exon for alternative splicing and is more widely expressed than previously thought...
- Binding of sodium channel inhibitors to hyperpolarized and depolarized conformations of the channelN Lenkey
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, P O B 67, H 1450 Budapest, Hungary
Neuropharmacology 60:191-200. 2011....
- Evaluation of the pharmacological activity of the major mexiletine metabolites on skeletal muscle sodium currentsM De Bellis
Unit of Pharmacology, Department of Pharmacobiology, University of Bari, Bari, Italy
Br J Pharmacol 149:300-10. 2006..It is extensively metabolized in humans but little information exists about the pharmacodynamic properties of its metabolites...
- The mechanism of intrinsic amplification of hyperpolarizations and spontaneous bursting in striatal cholinergic interneuronsCharles J Wilson
Department of Biology, University of Texas at San Antonio, 6900 North Loop, 1604 West, San Antonio, Texas 78249, USA
Neuron 45:575-85. 2005....
- Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanismHon Kit Wong
Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
Hum Mol Genet 17:3223-35. 2008..In conclusion, we believe that chemical compounds that target ASIC1a or pharmacological alleviation of UPS inhibition would be an effective and promising approach to combat HD and other polyQ-related disorders...
- Inhibition of membrane Na+ channels by A type botulinum toxin at femtomolar concentrations in central and peripheral neuronsMin Chul Shin
Research Division for Life Sciences, Kumamoto Health Science University, Japan
J Pharmacol Sci 118:33-42. 2012..The results suggest evidently that A2NTX could be also used as a powerful drug in treating epilepsy and several types of pain...
- Ranolazine: an antianginal drug with antiarrhythmic propertiesJuan Tamargo
Department of Pharmacology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain
Expert Rev Cardiovasc Ther 9:815-27. 2011..This article reviews the role of the I(NaL) and provides an update on experimental and clinical evidence supporting the efficacy and safety of ranolazine across a broad spectrum of arrhythmias...
- Clinical and electrocardiographic predictors of positive response to the intravenous sodium channel blockers in patients suspected of the Brugada syndromeShahab Shahrzad
Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Tehran University of Medical Sciences, Tehran, Iran
Int J Cardiol 165:285-90. 2013b>Sodium channel blockers are used to unmask the diagnostic ECG pattern of the Brugada syndrome (BrS) in case of a non-diagnostic baseline ECG...
- Effects of the NA+ channel blocker pilsicainide on the electrophysiologic properties of pulmonary veins in patients with atrial fibrillationKoichiro Kumagai
Department of Cardiology, Fukuoka University Hospital, Fukuoka, Japan
J Cardiovasc Electrophysiol 15:1396-401. 2004..The aim of the present study was to evaluate the effect of the pure Na+ channel blocker pilsicainide on the PVs...
- Selective targeting of sodium channel blockers to pain-sensing neuronsBruce P Bean; Fiscal Year: 2012..The overall goal of the proposed research is to identify combinations of TRPV1 activators and charged sodium channel blockers that optimize the block of excitability of nociceptive sensory neurons...
- Ion Selective Quantum Dots for Intracellular Mapping of Sodium Sparks in Cardiac Heather A Clark; Fiscal Year: 2012..Sodium sparks will be identified in cardiac myocytes, and will be evaluated for effects to sodium channel blockers. PUBLIC HEALTH RELEVANCE: The ultimate goal of this application is to develop and use a new intracellular ..
- The Development Epithelial Sodium Channel Blockers for Chronic Dry EyeBenjamin Yerxa; Fiscal Year: 2011..KCS/DED results from inadequate aqueous tear fluid on the eyes. Parion Sciences is developing a novel therapeutic agent that is predicted to provide long acting relief from dry eye symptoms. ..
- The Development Epithelial Sodium Channel Blockers for Chronic Dry EyeKARL H DONN; Fiscal Year: 2010..KCS/DED often results from inadequate aqueous tear fluid on the eyes. Parion Sciences is developing a novel therapeutic agent that is predicted to provide long acting relief from dry eye symptoms. ..
- PROLONGED DURATION LOCAL ANESTHESIADaniel S Kohane; Fiscal Year: 2013..of this research is to develop particulate prolonged duration local anesthetics (PDLA) employing site 1 sodium channel blockers such as saxitoxin (STX)...
- MODULATION OF CARDIAC REPOLARIZATIONDan M Roden; Fiscal Year: 2013..of sodium channel function predisposes to sudden death due to ventricular fibrillation: this is seen with sodium channel blockers in patients convalescing from acute myocardial infarction and with mutations that reduce cell surface ..
- Development of Novel Approaches for the Pharmacologic Treatment of Atrial FibrillCharles Antzelevitch; Fiscal Year: 2013..5) assess the effectiveness of different classes of sodium channel blockers in terminating and suppressing re-induction of AF, determine to what extent these agents are atrial-..
- Harnessing gating-pore currents to identify novel Nav1.7 modulatorsTheodore R Cummins; Fiscal Year: 2012..However, although sodium channel blockers are useful for preventing acute pain, they are often associated with undesirable cardiac and CNS side ..
- DEVELOPMENT OF NOVEL ANTIEPILEPTIC DRUGSManoj K Patel; Fiscal Year: 2010..pharmacology that has been well documented in temporal lobe epilepsy, reducing the efficacy of the sodium channel blockers in suppressing epileptic seizures...
- Annulation Strategies Toward the Total Synthesis of Saxitoxin and Zetekitoxin ABMichael R Krout; Fiscal Year: 2011..Guanidinium alkaloids saxitoxin and zetekitoxin AB are potent voltage-gated sodium channel blockers that pose significant synthetic challenges...
- MOLECULAR PHYSIOLOGY OF HYPERKALEMIC PERIODIC PARALYSISLawrence Hayward; Fiscal Year: 2001..b>Sodium channel blockers or other drugs will be compared for effectiveness in preventing abnormal muscle excitation or ..
- CONOPEPTIDE SODIUM CHANNEL BLOCKERS FOR CHRONIC PAINJames Garrett; Fiscal Year: 2000..4. Express various Na channels (PN3, SNS2, SkM1, BIIA [already on hand] and cardiac H1 [in process of obtaining]) in Xenopus oocytes and screen PN3-promising candidates for non-selectivity. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE ..
- DEVELOPMENT OF EPITHELIAL SODIUM CHANNEL BLOCKERS FOR CFJudith St George; Fiscal Year: 2006..Ultimately, our goal is the full clinical development of 552-02 as a first line therapy for patients suffering from CF airways disease [unreadable] [unreadable]..
- PROLONGED DURATION LOCAL ANESTHESIADANIEL KOHANE; Fiscal Year: 2004..take advantage of synergistic interactions between conventional amino amide local anesthetics and site 1 sodium channel blockers, as well as the potentiating effect of adjuncts such as glucocorticoids...
- INTERACTION OF ISCHEMIA, DRUGS, AND RATE ON CONDUCTIONWayne Cascio; Fiscal Year: 1991..aiNa, aiH+ and possibly aiCa++ at different stimulation rates both in the presence and absence of sodium channel blockers and simulated ischemia...
- NEUROTRANSMITTERS AND BRAIN INJURYMARK ZORNOW; Fiscal Year: 2000..examine effects of agents that may attenuate EAA release, including N-type calcium channel antagonists, sodium channel blockers, and adenosine A1 agonists on MRI-derived indices of intracellular swelling, histologic outcome, and ..
- IONIC CURRENTS AND (CA++)I IN CORONARY SMOOTH MUSCLEJames Johns; Fiscal Year: 1992..currents using a model similar to that of the Modulated Receptor Hypothesis, to explain the action of sodium channel blockers. The proposed area of research is an important area from both a clinical and a basic science standpoint...
- THERAPEUTIC NA+ CHANNEL BLOCKERS: RECEPTOR & DRUG DESIGNGING WANG; Fiscal Year: 2007..Such drugs, either taken orally or injected locally, may be beneficial for patients with chronic and intractable cancer pain. ..
- MOLECULAR BASIS OF LIGAND/SODIUM CHANNEL INTERACTIONSGING WANG; Fiscal Year: 2002....
- RVM CCK and Neuropathic PainJosephine Lai; Fiscal Year: 2007..In this regard, the proposed experiments may reveal an important role for CCK receptor antagonists as therapy for neuropathic pain. ..
- PHARMACOLOGY OF CARDIAC SODIUM CHANNEL MODIFIERSMichael Sheets; Fiscal Year: 2008..The results of these studies should improve our overall understanding of the molecular mechanisms of anti-arrhythmic drugs modification of cardiac Na channels. [unreadable] [unreadable]..
- SELECTIVE BLOCKADE OF TTX-R SODIUM CHANNELS FOR PAINJosephine Lai; Fiscal Year: 2001..These studies may have great practical significance towards the development of an effective therapy for neuropathic pain with few, or no, side effects. ..
- Afferent modulation in bladde dysfunctionNaoki Yoshimura; Fiscal Year: 2007..abstract not provided ..
- Development of isoform specific sensory neuronal sodium channel blockersTHEODORE CUMMINS; Fiscal Year: 2008..electrical activity of sensory neurons has been hindered by the lack of isoform specific neuronal sodium channel blockers. The goal of this R21 grant proposal is to develop selective sodium channel blockers based on biological ..
- Lower urinary tract dysfunction in Parkinson's diseaseNaoki Yoshimura; Fiscal Year: 2003..This is a high priority in the urologic care of patients with Parkinson's disease. ..
- Dietary Omega-3 Fatty Acids and Sudden Cardiac DeathGEORGE EDWARD BILLMAN; Fiscal Year: 2010..This project will also determine the effectiveness of fish oil supplements in reducing sudden death due to a lethal abnormal heart rhythm after a heart attack. ..
- MOLECULAR MECHANISMS OF HEXACARBON-INDUCED AXON ATROPHYRICHARD LOPACHIN; Fiscal Year: 2009..Understanding the role and mechanism of axon atrophy in solvent neurotoxicity has broad-based implications for human occupational health and risk assessment. ..
- Bladder Pain Gene Therapy with Pro-opiomelanocortin cDNANaoki Yoshimura; Fiscal Year: 2004..This research project is important to provide a solid basis for potential future clinical application. ..
- Mechanisms Underlying Rhythm Generation in Identified Spinal Interneurons in MiceLea Ziskind Conhaim; Fiscal Year: 2010....
- Neurophysiology and Biomechanics of Urethra in Stress Urinary IncontinenceNaoki Yoshimura; Fiscal Year: 2008..This is recognized as a high priority in the urologic/gynecologic care of SUI patients. [unreadable] [unreadable]..
- CARDIAC NA+ CHANNEL GATING AND LOCAL ANESTHETIC BLOCKSTERLING WRIGHT; Fiscal Year: 2004..abstract_text> ..
- AFFERENT PLASTICITY UNDERLYING URETHRAL AND PELVIC PAINNaoki Yoshimura; Fiscal Year: 2010..This is recognized as a high priority in the urologic care of patients with IC/CPPS. ..
- TRAINING IN MOLECULAR NEUROBIOLOGYWilliam Catterall; Fiscal Year: 2008..The training program will integrate the substantial expertise of this group of faculty in a coordinated pre-doctoral and post-doctoral training effort. ..
- Effect of Daily Exercise on Cardiac Autonomic RegulationGEORGE BILLMAN; Fiscal Year: 2005..Ventricular contractile responses to Beta1- and Beta2-adrenoceptor stimulation will be examined in vivo by echocardiography and in vitro by single cell fluorescence microscopy/video edge detection. ..
- Mode of Action of Insecticides: ElectrophysiologicalToshio Narahashi; Fiscal Year: 2004..This information will significantly contribute to the development of newer therapeutic means of insecticide intoxication of humans and of more effective and safer insecticides. ..
- CHARGED DIHYDROPYRIDINES--PROBES OF HEART CA++ CHANNELSRobert Kass; Fiscal Year: 2001....
- Development of Sensory/Pain-Selective Local AnestheticsPeter Gerner; Fiscal Year: 2006..abstract_text> ..
- Mechnaisms of Late Sodium Current in Failing HeartAlbertas Undrovinas; Fiscal Year: 2006..Knowledge derived from the present proposal may reveal novel targets for the treatment of life-threatening arrhythmias associated with chronic HF. ..
- Abused Inhalant Actions at GABA and Glutamate SynapsesM MacIver; Fiscal Year: 2008..Taken together, the results will allow a quantitative comparison of drug effects on glutamate and GABA-mediated transmission for commonly abused solvents including: toluene, 1,1,1-trichloroethane andtrichloroethylene. ..
- Automated Storage and Retrieval of Biological SystemsDan Roden; Fiscal Year: 2008..Accordingly, this proposal requests a high end instrument to accomplish these goals, and to thereby enable a new era of Personalized Medicine. [unreadable] [unreadable] [unreadable] [unreadable]..
- ACUTE BRAIN INJURY, MECHANISMS AND PROTECTIONJohn Olney; Fiscal Year: 2001..The long term goals are to clarify the underlying mechanisms and develop improved methods of treating human pediatric acute brain injury conditions. ..
- NEUROBIOLOGICAL EFFECTS OF ALTERED MOTOR CONTROL IN REMLARRY SANFORD; Fiscal Year: 2001..These studies may lead to a better understanding of disorders of REM, such as REM behavior disorder, which, like REM-A, is characterized by overt behavior during sleep. ..
- NEURAL MECHANISMS OF VENTRICULAR ELECTRICAL REMODELINGPhilip Adamson; Fiscal Year: 2003..These clinically applicable interventions may modify the natural history of diseases, such as heart failure, characterized by ventricular electrical remodeling leading to a high risk for lethal arrhythmias. ..
- DEVELOPMENTAL BRAIN DAMAGE BY DRUGS OF ABUSEJohn W Olney; Fiscal Year: 2010..abstract_text> ..
- NEURONAL ORGANIZATION OF BASAL GANGLIACharles Wilson; Fiscal Year: 2003..This latter will allow us to determine whether there is an actual mismatch between physiological and anatomical estimates of connectivity (i.e. non-functional synaptic connections). ..
- Glutamate Uptake & the Pathogenesis of Neuropathic PainJianren Mao; Fiscal Year: 2007..abstract_text> ..
- Temporal Transcriptomes of TBI and OGD for Dissemination (T3OD)Barclay Morrison; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Role of DEG/ENaC in the renal myogenic responseNIKKI JERNIGAN; Fiscal Year: 2005..abstract_text> ..
- NEURAL CIRCUITRY OF SENSORIMOTOR GATING ACROSS SPECIESNeal Swerdlow; Fiscal Year: 2006....
- Renal Epithelial Sodium Channels and SyntaxinsSunil Saxena; Fiscal Year: 2006..Epitope mapping will be used to optimize the specificity of polyclonal antibodies, and anti-sense oligonucleotides will be used to modulate the level of endogenous proteins in the mpkCCDC14 line. ..
- Regulation of ENaC by Serine Proteases in AirwaysScott Donaldson; Fiscal Year: 2006..The PI's long term goals are to provide important new insights into the basic elements of airway defense, CF lung disease, and to bring these findings to the development of novel therapies for CF lung disease. ..
- Neuroscience at the Boundaries of Neurology and PsychiatryNeal Swerdlow; Fiscal Year: 2006..unreadable] [unreadable]..
- Cerebellar Circuitry and Plasticity in an Electric FishVictor Han; Fiscal Year: 2007..The primary method will be whole-cell patch recordingin in vitro slices, combined with labelingof recorded elements for morphologicalidentification. ..
- A Simple Measure for Studying Sensory Gating DeficitsNeal Swerdlow; Fiscal Year: 2007..abstract_text> ..
- Inherited Ion Channel Defects in ArrhythmiasAUGUSTUS GRANT; Fiscal Year: 2005..Isoform expression will be determined by in situ hydridization. The proposed studies will provide new insights into ion channel function, their regulation and possible basis for cardiac arrhythmias. ..
- The Structure and Gating of the Epithelial Na+ ChannelOSSAMA KASHLAN; Fiscal Year: 2005..Such a map will help to delineate which amongst the currently proposed models for ENaC gating is most likely ..
- Membrane Transport of NH3 and NH4+NAZIH NAKHOUL; Fiscal Year: 2008..These are new properties of NH3/NH4+ transport that will help explain the role of NH3 and NH4+ in acidosis and their effect on transport of other ions a well. ..
- Biologic Ventricular Assist DeviceRobert Kloner; Fiscal Year: 2004..Identification and characterization of transplants will be carried out with PCR analysis of the Y chromosome (male cells into female host), detailed histologic analysis and immunostaining for muscle cell markers. ..
- MECHANISMS AND SITES OF VENTILATORY NEUROGENESISWALTER ST JOHN; Fiscal Year: 2008..Such information might provide insights into dysfunctions of the control of ventilation in humans, such as in "sleep apnea" or the "sudden infant death syndrome." [unreadable] [unreadable] [unreadable]..
- Inflammation-Induced Plasticity in Sensory NeuronsMichael Gold; Fiscal Year: 2006..unreadable] [unreadable] [unreadable]..
- Development of an electrical diagnostic for melanomaRichard Nuccitelli; Fiscal Year: 2008..If the handheld BFI is able to reliably detect malignant skin lesions, it will improve the quality of life for tens of thousands of dermatology patients in the United States alone. [unreadable] [unreadable] [unreadable]..
- MECHANISM OF INHIBITION OF CFTR BY AMP-ACTIVATED KINASEKENNETH HALLOWS; Fiscal Year: 2005..A final goal is to extend the search for functional effects of AMPK to transport systems that are closely associated with and modulated by CFTR. ..