ELECTROPHYSIOLOGICAL CORRELATES OF VASOPRESSIN RELEASE

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The goal is to understand how vasopressin (also called antidiuretic hormone) secretion is controlled through the control of the electrical firing patterns of vasopressin-secreting neurons. To achieve this goal, firing patterns of these neurons are correlated with vasopressin release in a model in vitro system, the rat supraoptico-neurohypophysial system, where firing patterns can be altered by neuroactive compounds which represent the neurotransmitter control of these neurons in the whole animal. Specific goals are 1) to relate the actions of histamine and noradrenaline on vasopressin release to their actions on bursts of electrical activity in supraoptic neurosecretory neurons; 2) to determine if different isoreceptors of these compounds mediate different actions; 3) to determine the interaction of these compounds with the electrical state of the neurosecretory neuron in evoking bursts of electrical activity; 4) to concisely localize the effects of these compounds on vasopressin and oxytocin neurons using intracellular labelling and immunocytochemistry; 5) to begin characterization of the membrane events related to the action of these compounds with intracellular recordings; and 6) to determine the quantitative relationship between a burst of activity in a vasopressin neuron and the amount and time course of vasopressin release. These aims will be realized by employing electrophysiology, neuropharmacology, immunocytochemistry and radioimmunoassay. The model system described herein provides a means of studying the relationship of electrical activity and hormone release. It is now known that many cells, non-neuronal in nature, also exhibit electrical activity when releasing hormone, and the questions answered by these studies could well be applicable to many cell types in the body. Vasopressin in particular is very important in determining proper water balance in all mammals, including man, and dysfunctions in its control lead to many physiological irregularities, including diabetes insipidus and chronic hypernatremia.