The Na+,K+ ‐ATPase: A Plausible Trigger for Voltage‐Independent Release of Cytoplasmic Neurotransmitters

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Abstract
A comparison was made between the releasability of 8 neurotransmitters from 8 regions of mouse brain in response to either 60 mM-K+ or 20 .mu.M-ouabain, a specific inhibitor of the Na+, K+-ATPase. With few exceptions, all transmitters were released by either or both agents from each brain region examined. K+ was superior in releasing the biogenic amines and acetylcholine, while the putative amino acid transmitters were generally releasable by both agents. Measurements of tissue depolarization using [3H]-tetraphenylphosphonium uptake indicated that 60 mM-K+ is capable of depolarizing brain tissue above the threshold necessary for initiating an action potential, but 20 .mu.M-ouabain is not. The pattern of release by ouabain coupled with its failure to depolarize brain tissue at 20 .mu.M suggests that inhibition of the Na+, K+-ATPase is capable of releasing cytoplasmic neurotransmitters in a voltage-independent manner.