VESICULAR AND CARRIER-MEDIATED DEPOLARIZATION-INDUCED RELEASE OF [H-3] GABA - INHIBITION BY AMILORIDE AND VERAPAMIL

The Ca2+-dependent, presumably exocytotic fraction of the [H-3]GABA re leased by depolarization is dissected from the depolarization-induced Na+-dependent, carrier-mediated fraction of [H-3]GABA release in mouse brain synaptosomes. GABA homoexchange is prevented by the [H-3]GABA c arrier blocker, DABA. The absence of external Na+ completely abolishes the release of the carrier-mediated, presumably cytoplasmic release o f [H-3]GABA induced by homoexchange and heteroexchange with GABA and D ABA, respectively. The carrier-mediated, Na+-dependent fraction of the depolarization-induced release of [H-3]GABA is resistant to tetrodoto xin (TTX) but is sensitive to amiloride and verapamil. The Ca2+-depend ent fraction of the [H-3]GABA released by high K+ depolarization is al so completely abolished by amiloride (from 300 muM) and sensitive to v erapamil (30 muM), but in contrast is insensitive to the absence of ex ternal Na+ and to DABA. On the basis of these results we conclude that amiloride and verapamil inhibit high K+-induced release of [H-3]GABA by antagonizing the entrance of Ca2+ (and possibly Na+ when external C a2+ is absent) through a population of voltage sensitive presynaptic C a2+ channels activated by depolarization.