Multiple voltage-sensitive calcium channels are probably involved in endogenous GABA release from striatal neurones differentiated in primary culture.
Calcium-dependent release of neurotransmitters is thought to be due to Ca2+ entry into nerve terminals, but the identities of the various voltage-sensitive Ca2+ channels (VSCC) involved in this process remain obscure. To elucidate the types of VSCCs involved in the release process, we studied the effects of various organic Ca2+ channel antagonists and agonists on the release of endogenous gamma-aminobutyric acid (GABA) from mouse striatal neurones differentiated in primary culture. Diltiazem, verapamil and methoxyverapamil (D 600) inhibited K+-evoked (30 mM) GABA release at very high concentrations (greater than 1 microM). The dihydropyridine (DHP) nifedipine, at low concentrations (0.01-1.00 microM), was able to inhibit part of the K+-evoked GABA release (25.6 +/- 7.3% inhibition at 1 microM). This is in agreement with the high affinity of nifedipine for DHP binding sites. The DHPs, BAY K 8644 (EC50 = 41 +/- 15 nM) and CGP 28.392, which possess agonist properties at VSCCs, increased the 15 mM K+-evoked GABA release. The release evoked by the combination of K+ (15 mM) and BAY K 8644 (up to 10 microM) remained smaller than the release elicited by 30 mM K+. The effect of BAY K 8644 (1 microM) was inhibited by nifedipine (IC50 0.55 +/- 0.05 microM). When Na+ ions were replaced by choline, basal and K+-evoked GABA release was significantly increased. Even in the absence of external Na+, nifedipine (1 microM) was not able to totally block the K+ effect. Moreover amiloride, a drug known to inhibit Na+/Ca2+ exchange, and tetrodotoxin (TTX), did not modify the 30 mM K+ response.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology*; D004563:Electrochemistry; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009411:Nerve Endings / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007473:Ion Channels; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D011188:Potassium; D002118:Calcium