Characterization of the type of calcium channel primarily regulating GABA exocytosis from brain nerve endings |
| |
Authors: | María Sitges Luz María Chiu |
| |
Institution: | (1) Instituto de Investigaciones Biomédicas, Depto. de Biología Molecular, UNAM, Ciudad Universitaria, Apartado Postal 70228, 04510 México, D.F. |
| |
Abstract: | In an attempt to further characterize the type of Ca2+ channels primarily regulating GABA exocytosis, the effects of increasing concentrations of CTx MVIIC,--Aga IVA and other Ca2+ channel blockers (nitrendipine, Cd2+ and Ni2+), commonly used for pharmacologically discerning among the various types of Ca2+ channels, were tested on the dissected Ca2+ dependent fraction of the depolarization evoked release of GABA from mouse brain synaptosomes. Our results show that -CTx MVIIC inhibits GABA exocytosis with a calculated IC50 of 3 M and -Aga IVA with a calculated IC50 of 50 nM. The divalent cation Cd2+ only diminishes GABA exocytosis at 70 M, but does not modify this response at lower concentrations (i.e. 1 and 10 M). Neither nitrendipine (10 M) nor Ni2+ (100 M and 500 M) modified GABA exocytosis. The failure of nitrendipine at a high concentration to inhibit GABA exocytosis discards L-type Ca2+ channels as the main regulators of this response; likewise that of Ni2+ discards Ca2+ channels of the N-type, and the failure of nM concentrations of -CTx MVIIC or 500 M Ni2+, also discards alpha1A/Q-type Ca2+ channels as the main regulators of the GABA response. On the basis of these results and in particular of the higher potency of -Aga IVA than -CTx MVIIC, it is concluded that the type of Ca2+ channels that primarily determine the exocytosis of GABA belong to a P-like type of Ca2+ channels. |
| |
Keywords: | -Aga IVA" target="_blank">gif" alt="ohgr" align="BASELINE" BORDER="0">-Aga IVA -CTx MVIIC" target="_blank">gif" alt="ohgr" align="BASELINE" BORDER="0">-CTx MVIIC nitrendipine Cd2+ Ni2+ synaptosomes |
本文献已被 SpringerLink 等数据库收录! |
|