The posterior pituitary is formed by nerve terminals emanating from the hypothalamus. The posterior pituitary releases two peptide hormones, vasopressin, which regulates blood circulation and renal function, and oxytocin, which regulates various reproductive functions. The nerve terminals of the posterior pituitary are unusually large, making them ideal for experimentation with patch clamp and imaging techniques. This provides a unique opportunity to investigate basic mechanisms underlying the regulation of neurosecretion. The present plan continues an investigation of membrane excitability in the posterior pituitary, emphasizing two recently discovered aspects of ion channel modulation. The first of these involves the labile gaseous signaling molecule nitric oxide (NO), which modulates ion channels in the posterior pituitary. Experiments will explore how NO and the NO signaling cascade modulate ion channels. The second involves sigma receptors, which modulate posterior pituitary ion channels in response to a number of ligands, including antipsychotic and psychotomimetic drugs. NO and sigma receptors employ novel mechanisms in the modulation of ion channels, and represent important additions to the repertoire of signaling pathways that affect electrical excitability. These mechanisms of ion channel modulation take on added significance in the context of the posterior pituitary, because they contribute to the regulation of neurosecretion. This study will examine how alterations in channel function influence action potential shape, calcium entry, and the propagation of electrical impulses through the complex terminal arborizations of the posterior pituitary. These factors influence release in profoundly different ways. Thus, this project will test basic hypotheses about how chemical signaling controls neurosecretion. Since axons generally extend over considerable distances, exhibit complex geometries, and have very large numbers of secretory specializations, these studies of the relationship between axonal geometry and ion channel modulation will have broad implications for the role of axon terminals in neural circuit function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
3R37NS030016-10S1
Application #
6469112
Study Section
Special Emphasis Panel (ZRG1 (01))
Program Officer
Talley, Edmund M
Project Start
1992-01-01
Project End
2004-11-30
Budget Start
2001-02-06
Budget End
2001-11-30
Support Year
10
Fiscal Year
2001
Total Cost
$17,904
Indirect Cost
Name
University of Wisconsin Madison
Department
Physiology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Johannessen, Molly; Fontanilla, Dominique; Mavlyutov, Timur et al. (2011) Antagonist action of progesterone at ýý-receptors in the modulation of voltage-gated sodium channels. Am J Physiol Cell Physiol 300:C328-37
Zhang, Zhenjie; Bhalla, Akhil; Dean, Camin et al. (2009) Synaptotagmin IV: a multifunctional regulator of peptidergic nerve terminals. Nat Neurosci 12:163-71
Dean, Camin; Liu, Huisheng; Dunning, F Mark et al. (2009) Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release. Nat Neurosci 12:767-76
Johannessen, Molly; Ramachandran, Subramaniam; Riemer, Logan et al. (2009) Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems. Am J Physiol Cell Physiol 296:C1049-57
Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R et al. (2009) The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science 323:934-7
Chang, Payne Y; Taylor, Portia E; Jackson, Meyer B (2007) Voltage imaging reveals the CA1 region at the CA2 border as a focus for epileptiform discharges and long-term potentiation in hippocampal slices. J Neurophysiol 98:1309-22
Zhang, Zhenjie; Klyachko, Vitaly; Jackson, Meyer B (2007) Blockade of phosphodiesterase Type 5 enhances rat neurohypophysial excitability and electrically evoked oxytocin release. J Physiol 584:137-47
Jackson, Meyer B (2007) In search of the fusion pore of exocytosis. Biophys Chem 126:201-8
Chang, Payne Y; Jackson, Meyer B (2006) Heterogeneous spatial patterns of long-term potentiation in rat hippocampal slices. J Physiol 576:427-43
Wang, Chih-Tien; Bai, Jihong; Chang, Payne Y et al. (2006) Synaptotagmin-Ca2+ triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation. J Physiol 570:295-307

Showing the most recent 10 out of 37 publications