Halothane and sevoflurane inhibit Na/Ca exchange current in rat ventricular myocytes

The electrogenic Na+/Ca2+ exchanger (NCX) represents the main extrusion pathway for Ca2+ in ventricular muscle and therefore plays an important role in the regulation of cytosolic Ca2+ and contraction. Halothane and sevoflurane modulate cytosolic Ca2+ regulation and at steady state are negatively inotropic, however, the involvement of anaesthetic-induced changes in NCX activity in these effects requires further study.

Ventricular myocytes were isolated using a standard collagenase/protease dispersion technique and superfused with a physiological salt solution at 30 degrees C. Whole-cell patch-clamp technique was used to control membrane voltage. I(NCX) (identified as Ni2+ sensitive current) was recorded using a ramp clamp protocol under conditions to inhibit contaminating currents.

With 0.6 mM sevoflurane, outward I(NCX) at positive voltages (> or = 0 mV) and inward I(NCX) at voltages negative to -60 mV was significantly reduced (P<0.05, n=13; I(NCX) reduced by 48% at +50 and 65% of control at -120 mV). Halothane (0.6 mM) inhibited outward I(NCX) at voltages positive to -10 mV and inward I(NCX) at voltages negative to -80 mV (P<0.05, n=10; I(NCX) reduced by 64% at +50 and 65% of control at -120 mV). Anaesthetic-induced inhibition of both inward and outward current was not voltage-dependent.

Inhibition of Ca2+ efflux via NCX (i.e. inward I(NCX)) during an exposure to halothane or sevoflurane would be expected to limit the negative inotropic effects of these agents and help maintain SR Ca2+ content.