MEMBRANE EXCITABILITY AND SECRETION FROM NERVE ENDINGS

Summary

Principal Investigator: Meyer Jackson
Abstract: DESCRIPTION: Patch clamp techniques will be used to investigate the regulation of secretion from nerve terminals of the posterior pituitary (neurohypophysis). These nerve terminals secrete two neuropeptides, vasopressin, which is involved in cardiovascular function, and oxycytocin, which is involved in reproductive function. In thin slices, single nerve terminals are accessible to patch clamp techniques, making it possible to study cellular and molecular mechanisms of secretion. Opioid and dopamine receptors can be activated to enhance or inhibit neuropeptide release from the posterior pituitary. Experiments proposed will investigate the consequences of activation of these receptors in pituitary nerve terminals, and elucidate the underlying mechanisms of transduction. The ion channels coupled to these receptors will be identified and characterized. The mechanism of coupling between receptors and effectors will be investigated by clarifying the roles of G-proteins, protein kinases, and protein phosphatases. Hypotheses will be tested concerning the influence of action potential shape on secretion and the relationship between Ca2+ entry, changes in intracellular Ca2+ concentration, and hormone secretion. These experiments will provide a better understanding of how neurotransmitters regulate neuropeptide secretion from neurosecretory neurons. The results should also be relevant to broader issues of regulation of synaptic transmission, and how drugs act on presynaptic opioid and dopamine receptors. Experiments will also explore the mechanism by which Ca2+ triggers exocytosis, and how Ca2+-sensing proteins participate in this process. Quantitative kinetic techniques will be used to measure rates of secretion under defined levels of intracellular Ca2+. Reagents will be introduced that are specific for identified proteins believed to play critical roles in Ca2+-triggered secretion. Using reagents for CAPS and synaptotagmin, two proteins with demonstrated roles in neurosecretion, experiments will provide insight into how these proteins couple excitation and secretion in nerve endings. These issues are relevant not only to the physiological regulation of blood pressure and volume, lactation, and parturition, which are controlled by the two neurohypophysial hormones, but are also relevant to a broad class of systems in which synaptic plasticity occurs, and in which mechanisms of synaptic plasticity are believed to be presynaptic.
Funding Period: 1992-01-01 - 2000-11-30
more information: NIH RePORT

Top Publications

  1. ncbi Fusion pores and fusion machines in Ca2+-triggered exocytosis
    Meyer B Jackson
    Howard Hughes Medical Institute, 2Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA
    Annu Rev Biophys Biomol Struct 35:135-60. 2006
  2. pmc The fusion pores of Ca2+ -triggered exocytosis
    Meyer B Jackson
    Department of Physiology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA
    Nat Struct Mol Biol 15:684-9. 2008
  3. pmc Synaptotagmin-Ca2+ triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation
    Chih Tien Wang
    Department of Physiology, University of Wisconsin, Madison, 53706, USA
    J Physiol 570:295-307. 2006
  4. pmc Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release
    Camin Dean
    Department of Physiology, University of Wisconsin, Madison, Wisconsin, USA
    Nat Neurosci 12:767-76. 2009
  5. pmc Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems
    Molly Johannessen
    Dept of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Am J Physiol Cell Physiol 296:C1049-57. 2009
  6. pmc The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator
    DOMINIQUE FONTANILLA
    Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Science 323:934-7. 2009
  7. pmc Blockade of phosphodiesterase Type 5 enhances rat neurohypophysial excitability and electrically evoked oxytocin release
    Zhenjie Zhang
    Department of Physiology, University of Wisconsin, Madison WI, USA
    J Physiol 584:137-47. 2007
  8. ncbi Voltage imaging reveals the CA1 region at the CA2 border as a focus for epileptiform discharges and long-term potentiation in hippocampal slices
    Payne Y Chang
    Department of Physiology and Biophysics Program, University of Wisconsin Medical School, 1300 University Ave, SMI 127, Madison, WI 53706, USA
    J Neurophysiol 98:1309-22. 2007
  9. pmc Heterogeneous spatial patterns of long-term potentiation in rat hippocampal slices
    Payne Y Chang
    Department of Physiology, University of Wisconsin Madison, 1300 University Ave, Madison, WI 53706, USA
    J Physiol 576:427-43. 2006
  10. pmc In search of the fusion pore of exocytosis
    Meyer B Jackson
    Department of Physiology, University of Wisconsin, Wisconsin, USA
    Biophys Chem 126:201-8. 2007

Scientific Experts

  • Meyer Jackson
  • Payne Y Chang
  • Molly Johannessen
  • DOMINIQUE FONTANILLA
  • Arnold E Ruoho
  • Camin Dean
  • Edwin R Chapman
  • Zhenjie Zhang
  • Xue Han
  • Chih Tien Wang
  • Timur Mavlyutov
  • Andrea Ramos-Serrano
  • Huisheng Liu
  • Logan Riemer
  • F Mark Dunning
  • Subramaniam Ramachandran
  • Nicholas V Cozzi
  • Abdol R Hajipour
  • Portia E Taylor
  • Vitaly Klyachko
  • Jihong Bai

Detail Information

Publications12

  1. ncbi Fusion pores and fusion machines in Ca2+-triggered exocytosis
    Meyer B Jackson
    Howard Hughes Medical Institute, 2Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA
    Annu Rev Biophys Biomol Struct 35:135-60. 2006
    ..We summarize present knowledge of fusion machines and fusion pores studied in vitro, in neurons, and in neuroendocrine cells, and synthesize this knowledge into some specific and detailed hypotheses for exocytosis...
  2. pmc The fusion pores of Ca2+ -triggered exocytosis
    Meyer B Jackson
    Department of Physiology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA
    Nat Struct Mol Biol 15:684-9. 2008
    ....
  3. pmc Synaptotagmin-Ca2+ triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation
    Chih Tien Wang
    Department of Physiology, University of Wisconsin, Madison, 53706, USA
    J Physiol 570:295-307. 2006
    ..The C2A and C2B domains of Syt I have different actions during these steps, and these actions may be linked to their distinctive effector interactions...
  4. pmc Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release
    Camin Dean
    Department of Physiology, University of Wisconsin, Madison, Wisconsin, USA
    Nat Neurosci 12:767-76. 2009
    ..Thus, regulation of BDNF secretion by syt-IV emerges as a mechanism for maintaining synaptic strength in a useful range during LTP...
  5. pmc Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems
    Molly Johannessen
    Dept of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Am J Physiol Cell Physiol 296:C1049-57. 2009
    ..The modulation of Na(v)1.5 channels by sigma-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity...
  6. pmc The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator
    DOMINIQUE FONTANILLA
    Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Science 323:934-7. 2009
    ..DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor...
  7. pmc Blockade of phosphodiesterase Type 5 enhances rat neurohypophysial excitability and electrically evoked oxytocin release
    Zhenjie Zhang
    Department of Physiology, University of Wisconsin, Madison WI, USA
    J Physiol 584:137-47. 2007
    ..Thus, PDE5 plays an important role in the regulation of neurohypophysial function, and blockade of this enzyme can enhance the use-dependent facilitation of neurohypophysial secretion...
  8. ncbi Voltage imaging reveals the CA1 region at the CA2 border as a focus for epileptiform discharges and long-term potentiation in hippocampal slices
    Payne Y Chang
    Department of Physiology and Biophysics Program, University of Wisconsin Medical School, 1300 University Ave, SMI 127, Madison, WI 53706, USA
    J Neurophysiol 98:1309-22. 2007
    ..Thus the CA1 region at the CA2 border has unique properties, which make this part of the hippocampus an important locus for both epileptiform activity and plasticity...
  9. pmc Heterogeneous spatial patterns of long-term potentiation in rat hippocampal slices
    Payne Y Chang
    Department of Physiology, University of Wisconsin Madison, 1300 University Ave, Madison, WI 53706, USA
    J Physiol 576:427-43. 2006
    ..Thus, postsynaptic spikes during induction constitute a critical determinant for the expression of LTP in intact circuits...
  10. pmc In search of the fusion pore of exocytosis
    Meyer B Jackson
    Department of Physiology, University of Wisconsin, Wisconsin, USA
    Biophys Chem 126:201-8. 2007
    ..The fusion pore determines how rapidly neurotransmitter is expelled from a vesicle into the synaptic cleft. This rate places constraints on the form of a synaptic response during different modes of release...
  11. pmc Structural transitions in the synaptic SNARE complex during Ca2+-triggered exocytosis
    Xue Han
    Department of Physiology, University of Wisconsin Medical School, Madison, WI 53706, USA
    J Cell Biol 172:281-93. 2006
    ..The dependence of these three rate processes on position within the SNARE complex does not support vectorial SNARE complex zipping during exocytosis...
  12. pmc Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels
    Molly Johannessen
    Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Am J Physiol Cell Physiol 300:C328-37. 2011
    ....