Accelerating effects of pentobarbitone on the inactivation process of the calcium current in Helix neurones.

Abstract

The effect of pentobarbitone on Ca2+ current (ICa), separated from other ionic currents was studied under voltage clamp using a suction pipette technique in Helix neurones. Pentobarbitone depressed the maximal peak amplitude (MPA) of ICa in a concentration-dependent manner without shifting the current-voltage (I-V) relationships along the voltage axis. Increases in external Ca2+-concentration [( Ca2+]o) overcame the inhibitory action of the agent on MPA. Pentobarbitone markedly accelerated the decay phase of ICa which took a distinctly different time course from that of the control. The accelerating action of the agent on the decay phase of ICa was not overcome by increases in [Ca2+]o. In the presence of internal EGTA (20 mM), pentobarbitone also accelerated the decay of ICa. Changes in pH of the external perfusing solution altered the potency of pentobarbitone in depressing MPA; in the presence of pentobarbitone (3 X 10(-4) M) at pH of 7.0, 8.0 and 9.0, fractional inhibition was approx. 46%, 21% and 4%, respectively. Internal application of pentobarbitone (10(-4)-10(-3) M) inhibited MPA, but exerted no effect on the decay phase of ICa. Pentobarbitone (10(-4) M) markedly accelerated the decrease of MPA of ICa induced by repetitive stimuli applied at an interval of 150 ms, indicating a use-dependent depression of MPA. Results provide evidence that pentobarbitone has a dual action on ICa, inhibiting MPA and accelerating the decay phase of ICa.