Sustained GABA-induced regulation of the inactivation of the voltage-dependent Ca2+ current in crustacean muscle fibers

We describe a new form of gamma-aminobutyric acid (GABA) -mediated regulati on of the inactivation and of the recovery from inactivation of the L-type Ca2+ current (I-Ca) in crayfish muscle. GABA (1 mM) was applied during a 2- min period and the peak I-Ca was measured using two-electrode voltage-clamp recordings 30 min after returning to the control solution. Prepulse-pulse protocols showed that the GABA-mediated inhibition of I-Ca decreased (>50%) both with increasing prepulse depolarization and as the delay between prep ulse and pulse was reduced. GABA also shifted to depolarized values (>5 mV) the S-shaped plots of the peak I-Ca evoked by a constant depolarizing puls e as a function of prepulse voltage (i.e., inactivation curves) and acceler ated the recovery time from the inactivation evoked by depolarizing prepuls es (>35%). The effects outlasted GABA application up to 1 h. The observed c hanges in inactivation properties may be of functional importance because t hey indicate that previous depolarization relieves the GABA-induced inhibit ion of I-Ca, implying that this long-lasting inhibition is under the regula tion of the prepulse potential and the subsequent Ca2+ entry.