γ-Aminobutyric acid increases intracellular Ca 2+ concentration in cultured cortical neurons: role of Cl − transport

Abstract

The effect of γ-aminobutyric acid (GABA) on intracellular Ca 2+ concentration ([Ca 2+] i) in cultured prenatal rat cortical neurons was investigated using fluorescence imaging. GABA or muscimol, but not baclofen, increased [Ca 2+] i in a dose-dependent manner. The GABA A receptor antagonists, bicuculline and picrotoxin, inhibited the GABA response. Furosemide, an inhibitor of the Na +/K +/2Cl − cotransporter, inhibited the GABA response in a noncompetitive manner. Ethacrynic acid, an inhibitor of an ATP-dependent Cl − pump, also inhibited the GABA-induced increased in [Ca 2+] i. These results suggest a role for Cl − transport processes in the GABA response. The coapplication of GABA and high K + led to a non-additive increase in the GABA response. The GABA response was also inhibited by nifedipine, a voltage-gated Ca 2+ channel blocker, and abolished by the absence of extracellular Ca 2+. Results indicate that the GABA response shares a common pathway of Ca 2+ movement with the high K +-induced response. These observations suggest that the stimulation with GABA results in Ca 2+ influx through voltage-gated Ca 2+ channels, and that these effects are dependent on Cl − transport systems.