title: Isoflurane reduces Ca++ channel current and accelerates current decay in guinea pig portal vein smooth muscle cells.
abstract: 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.
authors.affiliation: Department of Anesthesiology, University of Michigan Medical Center, Ann Arbor.
authors.forename: D W
authors.initials: DW
authors.lastname: Wilde
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology
chemical_list: D015220:Calcium Channels; D007530:Isoflurane