Vesicular and carrier-mediated depolarization-induced release of [3H]GABA: inhibition by amiloride and verapamil.
The Ca(2+)-dependent, presumably exocytotic fraction of the [3H]GABA released by depolarization is dissected from the depolarization-induced Na(+)-dependent, carrier-mediated fraction of [3H]GABA release in mouse brain synaptosomes. GABA homoexchange is prevented by the [3H]GABA carrier blocker, DABA. The absence of external Na+ completely abolishes the release of the carrier-mediated, presumably cytoplasmic release of [3H]GABA induced by homoexchange and heteroexchange with GABA and DABA, respectively. The carrier-mediated, Na(+)-dependent fraction of the depolarization-induced release of [3H]GABA is resistant to tetrodotoxin (TTX) but is sensitive to amiloride and verapamil. The Ca(2+)-dependent fraction of the [3H]GABA released by high K+ depolarization is also completely abolished by amiloride (from 300 microM) and sensitive to verapamil (30 microM), but in contrast is insensitive to the absence of external Na+ and to DABA. On the basis of these results we conclude that amiloride and verapamil inhibit high K(+)-induced release of [3H]GABA by antagonizing the entrance of Ca2+ (and possibly Na+ when external Ca2+ is absent) through a population of voltage sensitive presynaptic Ca2+ channels activated by depolarization.
Sitges
M
M
División de Investigaciones Clínicas, Instituto Mexicano de Psiquiatría, SSA, D.F., México.
Chiu
L M
LM
González
L
L
D000584:Amiloride / Q000494:pharmacology*; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D051379:Mice; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D014700:Verapamil / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D015220:Calcium Channels; D014316:Tritium; C005959:2,4-diaminobutyric acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D000584:Amiloride; D012964:Sodium; D014700:Verapamil; D011188:Potassium; D002118:Calcium