omega-Aga IVA selectively inhibits the calcium-dependent fraction of the evoked release of [3H]GABA from synaptosomes.
The effect of omega-Aga IVA, a P-type Ca2+ channel blocker, on the release of the inhibitory neurotransmitter GABA and on the elevation of Cai induced by depolarization was investigated in [3H]GABA and fura-2 preloaded mouse brain synaptosomes, respectively. Two strategies (i.e. 20 mM external K+ and veratridine) that depolarize by different mechanisms the preparation were used. High K+ elevates Cai and induces [3H]GABA release in the absence of external Na+ and in the presence of TTX, conditions that abolish veratridine induced responses. The effect of omega-Aga IVA on the Ca2+ and Na+ dependent fractions of the depolarization evoked release of [3H]GABA were separately investigated in synaptosomes depolarized with high K+ in the absence of external Na+ and with veratridine in the absence of external Ca2+, respectively. The Ca2+ dependent fraction of the evoked release of [3H]GABA and the elevation of Ca2+ induced by high K+ are markedly inhibited (about 50%) in synaptosomes exposed to omega-Aga IVA (300 nM) for 3 min before depolarization, whereas the Na+ dependent, Ca2+ independent carrier mediated release of [3H]GABA induced by veratridine, which is sensitive to verapamil and amiloride, is not modified by omega-Aga IVA. Our results indicate that an omega-Aga IVA sensitive type of Ca2+ channel is highly involved in GABA exocytosis.
Sitges
M
M
Instituto de Investigaciones Biomédicas, México, D.F.
Chiu
L M
LM
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008978:Mollusk Venoms / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology*; D013111:Spider Venoms / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D008978:Mollusk Venoms; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D014316:Tritium; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D000584:Amiloride; D020866:omega-Conotoxin GVIA; D012964:Sodium; D011188:Potassium