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

Abstract.

We describe a new form of γ-aminobutyric acid (GABA) -mediated regulation 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 prepulse 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 pulse as a function of prepulse voltage (i.e., inactivation curves) and accelerated the recovery time from the inactivation evoked by depolarizing prepulses (>35%). The effects outlasted GABA application up to 1 h. The observed changes in inactivation properties may be of functional importance because they indicate that previous depolarization relieves the GABA-induced inhibition of I _Ca , implying that this long-lasting inhibition is under the regulation of the prepulse potential and the subsequent Ca²⁺ entry.