Isoflurane reduces Ca++ channel current and accelerates current decay in guinea pig portal vein smooth muscle cells

The volatile anesthetic isoflurane (ISO) can exert significant inhibitory effects on hemodynamics and organ perfusion. It was hypothesized that venodilation during ISO exposure was mediated through a reduction in inward Ca++ channel current. By using the whole cell mode of single cell patch clamp technique, the action of ISO on L-type Ca++ channel current was examined. ISO caused a concentration-dependent reduction in maximal Ca++ channel current and shifted the current activation to more negative potentials. ISO, 3%, shifted the voltage for half-maximal channel inactivation from -21.9 to -33.4 mV. Measurement of time constants for inward current activation and inactivation revealed that the inactivation phase exhibited a concentration-dependent reduction over the range of 0.36 to 3% ISO. The decrease in the inactivation time constant is consistent with accelerated inactivation of the L-channel current. Estimated binding constants for ISO to resting or inactivated channels suggest absence of state-dependent inhibition of channel conductance. The venodilatory effects of ISO are due in part to limitation of Ca++ influx which may secondarily affect Ca(++)-dependent mechanisms such as the outward Ca(++)-activated K+ channel population. Reduction in current by ISO may occur through receptor-independent mechanisms and may involve perturbation of the sarcolemmal lipid bilayer.