Veratridine-activated release of adenosine-5′-triphosphate from synaptosomes: Evidence for calcium dependence and blockade by tetrodotoxin

Cholinergic synaptosomes from squid brain were found to release almost 50% of their total endogenous ATP when exposed to veratridine, an alkaloid which activates action potential sodium channels in nervous tissue. Veratridine also depolarizes synaptosomes and induces transmitter release by a mechanism which is dependent upon free Ca⁺⁺ in the medium and is inhibited by tetrodotoxin, a specific veratridine inhibitor. ATP release activated by veratridine was also found to be calcium dependent and tetrodotoxin-sensitive. A new filter assay was developed to measure the kinetics of ATP release quantitatively, and veratridine-activated ATP release from synaptosomes was found to be complete in less than 30 seconds. Since ATP is a major component of cholinergic vesicles, this finding supports the concept that transmitter release from synaptosomes may occur from a vesicular rather than from a cytoplasmic pool.