SODIUM-DEPENDENT SECRETION AND RETENTION OF NE IN ADRENERGIC TERMINALS

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The following report represents continued research on a functional, physiologic neurosecretory system. Sodium can regulate a delayed, Ca-evoked, export-mediated secretion of [3H]norepinephrine ([3H]NE) in the adrenergic terminals in slices of rat heart. The secretion was interpreted to be an indication of Ca permeation through specific channels in the axolemma. Permeation through other channels did not necessarily evoke secretion. Secretion occurred in a medium (Ch-Ca) in which choline (not Li, K or sucrose) replaced the Na in a Krebs-bicarbonate medium. Choline in a limited way functioned a surrogate for Na as an extracellular requirement for retention. Like Na (Bogdanski and Brodie, 1969) choline (25 and 50 mM) in a sucrose medium inhibited the non-Ca dependent depletion of the [3H]NE. The choline (13OmM) in Ch-Ca, after a delay of 60 to 80 min, permitted Ca to evoke secretion. Its start was related to the length of the time period that the terminals had been exposed to choline, not Ca. Because secretion was prevented by Mn, lmM, it was concluded that a voltage regulated Ca channel might finally have opened. Secretion was stopped more rapidly after Na was added to the Ch-Ca than after the terminals were transferred to a Ca-deprived medium. Na thus appeared to act intracellularly. K (66mM) augmented maximal rates of secretion evoked by Ch-Ca with or without added Na. Apparently, the axolemma in Ch-Ca had been polarized and depolarization by K opened new Ca channels. Conclusions: Na at two or more sites in or proximate to the axolemma may partially regulate physiological secretion. First, choline representing physiological Na temporarily prevented spontaneous Ca entry through channels specific for secretion. This did not involve Na-Ca exchange. Second, Na in the axosol inhibited secretion. Malfunctions of either function could induce physiologically excessive, spontaneous release of transmitters.