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.
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