Quantitative Comparisons Between the Electrical Activity of Supraoptic Neurons and Vasopressin Release in vitro

Abstract The firing rate of antidromically identified neurons in the tuberal portion of the rat supraoptic nucleus and vasopressin release were compared in an in vitro preparation of the hypothalamo-neurohypophysical system. Extracellular potentials were isolated and held while the perifusing medium was collected for radioimmunoassay of vasopressin. Neurons in the tuberal portion of the supraoptic nucleus were induced to first bursts of action potentials by injecting supra-threshold concentrations (0.01, 0.1 and 1 mM) of the alpha(1)-agonist phenylephrine into the perifusing line. Phenylephrine caused a dose-dependent release of vasopressin into the perifusate and a dose-dependent increase in the peak firing rate, initial burst duration and the total number of action potentials (compared to a 10 min control period) of the recorded neurons. Peak firing rate and peak vasopressin release both increased linearly with the log of the phenylephrine dose, but the efficiency ratio of the increase in vasopressin release to the increase in firing rate was greater from the middle to the highest dose than it was for the lowest to the middle dose, indicating a possible facilitation of hormone release with higher firing frequencies. The total amount of vasopressin released in 10 min post-injection and the total number of evoked action potentials in the same period also increased linearly, but in this case there was no change in the efficiency ratio between the low to middle and the middle to high doses of phenylephrine. Release of vasopressin to phenylephrine was dependent on an intact neural stalk, and in a separate group of isolated neural lobes, 1 mM phenylephrine did not significantly alter the peak or total amount of vasopressin released to an electrical stimulus given in the pattern of an evoked burst. In another group of explants the temporal relationship between firing rate and vasopressin release was examined after a single dose of 1 mM phenylephrine. In these explants the true time-course of release was estimated using a deconvolution procedure which corrected for diffusion of the hormone. Mean vasopressin release and spike activity were still elevated above baseline 4 to 5 min after the first elicited burst, suggesting that the latter parts of the initial burst and/or the after-discharges contribute to the prolonged vasopressin release. However, there was a dramatic drop in the efficiency ratio (vasopressin release/peak firing rate) from the first to the second minute following stimulation. Thus, changes in the frequency of action potentials generated by supraoptic neurons can be directly related to simultaneous changes in the rate of vasopressin release in the same preparation. The results suggest that elevations in firing rate are accompanied by an increased rate of vasopressin release, but as has been demonstrated in isolated neural lobes, this relationship is probably not constant across different stimulation strengths or within a single burst.