Effect of organic and inorganic calcium channel blockers on gamma-amino-n-butyric acid release induced by monensin and veratrine in the absence of external calcium.
The effects of two organic Ca2+ antagonists (verapamil and nitrendipine) and of two inorganic Ca2+ channel blockers (Co2+ and ruthenium red) on the Na+-dependent release of gamma-amino-n-butyric acid (GABA) triggered by veratrine and monensin in the absence of external Ca2+ were studied in mouse brain synaptosomes. Ca2+-independent release of GABA stimulated by the Na+ channel activator veratrine was inhibited with micromolar concentrations of verapamil and nitrendipine. In contrast, GABA release induced by the Na+ ionophore monensin was insensitive to the organic Ca2+ antagonists. Verapamil also failed to modify A23187-stimulated release of GABA in the presence of Ca2+ but inhibited high K+-induced release of the transmitter. Co2+ partially diminished veratrine-induced release but did not change monensin-induced release. Releasing responses to monensin and veratrine were insensitive to ruthenium red, which inhibited the Ca2+-dependent component of GABA release evoked by high K+ depolarization. These data demonstrate that the mechanism of inducing GABA release is different for veratrine and monensin, as evidenced by their differing sensitivities to inhibition by Ca2+ channel antagonists and organic Ca2+ blockers. It is concluded that voltage-sensitive Ca2+ channels of the presynaptic membrane are not involved in the inhibitory action of Ca2+ antagonists on the Na+-dependent, Ca2+-independent mechanism of GABA release.
Sitges
M
M
Departamento de Neuroquímica, Instituto Mexicano de Psiquiatría, México.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D051379:Mice; D008985:Monensin / Q000494:pharmacology*; D009568:Nitrendipine / Q000494:pharmacology; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002121:Calcium Channel Blockers; D012430:Ruthenium Red; D000001:Calcimycin; D005680:gamma-Aminobutyric Acid; D008985:Monensin; D009568:Nitrendipine; D014700:Verapamil; D014702:Veratrine; D011188:Potassium