Reduction in the myocardial sodium current by halothane and thiamylal.
Effects of two general anesthetics, halothane and thiamylal, on the fast sodium inward current (INa) of enzymatically isolated single rat ventricular cells were studied under current clamp and voltage clamp conditions. A suction pipette technique was used for potential measurement, current injection and internal perfusion of isolated cells. In current clamp experiments, sodium action potential was elicited in a Ca-free Co Krebs solution and the action potential was reduced by 0.5% halothane and 5 X 10(-5) M thiamylal. In voltage clamp experiments, the calcium current was suppressed by replacing Ca with Co and the potassium current was eliminated by replacing K with Cs and adding 4-aminopyridine and tetraethylammonium. Both anesthetics decreased INa, in a dose dependent manner, without changing the shape of the current-voltage curve. Halothane (1%) shifted the steady state inactivation curve in a negative direction along the potential axis by 8.5 +/- 2 mV (mean +/- S.D., n = 4). Thiamylal, 5 X 10(-5) and 10(-4) M, shifted the curve in a negative direction by 4.4 +/- 0.8 mV (n = 5) and 8.6 +/- 3.2 mV (n = 5), respectively. Both agents slightly reduced the maximum sodium conductance (gNa). Halothane (1%) increased half recovery time from inactivation measured at -80 mV from 30 +/- 15 to 80 +/- 25 ms (n = 4). Thiamylal (10(-4) M) prolonged it at - 75 mV from 50 +/- 20 to 110 +/- 15 ms (n = 5). With a test pulse duration of 50 ms, neither drug produced a use-dependent inhibition of INa. Halothane and thiamylal depress the INa of cardiac muscles mainly by shifting the steady state inactivation curve in a negative direction along the potential axis. Relatively small prolongation of half recovery time from inactivation and no sign of use-dependent inhibition suggest a molecular mechanism which differs in some respects from the local anesthetics.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006221:Halothane / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D011690:Purkinje Fibers / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013840:Thiamylal / Q000494:pharmacology*
D007473:Ion Channels; D013840:Thiamylal; D012964:Sodium; D002118:Calcium; D006221:Halothane