Patch clamp techniques will be used to study excitability and secretion in nerve terminals of slices prepared from the rat posterior pituitary. The nerve endings of the posterior pituitary secrete the peptide hormones vasopressin and oxytocin. In thin slices, these nerve endings are accessible to patch clamp techniques, thus providing a new system for the investigation of presynaptic mechanisms. Secretion is stimulated by electrical activity, and is subject to regulation by a variety of physiologically important factors. The ion channels of the nerve terminal membrane play a key role in these processes by generating and shaping action potentials, and permitting Ca to enter. These ion channels will be studied with the goal of determining 1) how many potassium, sodium, and calcium channel subtypes are in the membranes of the nerve endings; 2) what their basic functional properties are; and 3) how selective channel blockers act on the different channel subtypes. Selective channel blockers and modeling techniques will then probe the function of each channel subtype. The role of each channel subtype in determining action potential shape will be examined. Hypotheses will be tested concerning the role of action potential shape and Ca channel properties in regulating Ca entry. Experiments will determine the relationship between Ca entry, changes in intracellular Ca concentration, and hormone secretion. These studies will provide basic insight into 1) the mechanism of stimulus-secretion coupling in nerve endings; 2) mechanisms of frequency coding of secretion; 3) the different mechanisms of regulation of secretion of vasopressin and oxytocin; and 4) the mechanisms by which opioid peptides modulate secretion. These results are relevant not only to the physiological regulation of blood pressure, lactation, and parturition, which are controlled by the neurohypophysial hormones, but are also relevant to a broad class of systems in which synaptic plasticity occurs, and in which the mechanism of synaptic plasticity is believed to be presynaptic.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS030016-01
Application #
3416941
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1992-01-01
Project End
1995-12-31
Budget Start
1992-01-01
Budget End
1992-12-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
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
Jackson, Meyer B; Chapman, Edwin R (2008) The fusion pores of Ca(2+)-triggered exocytosis. Nat Struct Mol Biol 15:684-689
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

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