Effects of halothane on the transient outward K+ current in rat ventricular myocytes

1 Halothane has been shown to affect several membrane currents in cardiac t issue including the L-type calcium current (I-Ca), sodium current and a var iety of potassium currents. However, little is known about the effects of h alothane on the transient outward K+ current (I-to). 2 Single ventricular myocytes from rat hearts were voltage clamped using th e whole cell patch configuration and an EGTA-containing pipette solution to record the Ca2+-independent, 4-aminopyridine sensitive component of I-to. 300 mu M Cd2+ or 10 mu M nifedipine was used to block I-Ca. 3 At +80 mV, I-to (peak current minus current at the end of the pulse) was 1.8+/-0.2 nA under control conditions which was reduced to 1.3+/-0.2 nA by 1 mM halothane (P<0.001, mean+/- s.e.mean, n = 9). The inhibition of I,, by halothane was concentration-dependent (K-0.5, 1.1+/-0.2 mM). One mM haloth ane led to a 16 mV shift in the steady-state inactivation curve towards neg ative membrane potentials (P=0.005, n=8) but had no significant effect on t he activation-voltage relationship (P = 0.724). 4 One mM halothane also increased the rate of inactivation of I,,; the domi nant time constant of inactivation was reduced from 14+/-1 to 9+/-1 ms (P=0 .017, mean+/-s.e.mean, n=6). 5 These data show that halothane reduced I-to; 0.3 mM, close to the MAC(50) value for halothane, inhibited the current by 15% and as such, the inhibit ion of I,, will be relevant to the clinical situation. Halothane induced a shift in the steady-state inactivation curve and accelerated the inactivati on process of I-to which could be responsible for its inhibitory effect. 6 Due to the differential transmural expression of I-to in ventricular tiss ue, inhibition of I-to would reduce the transmural dispersion of refractori ness which could contribute to the arrhythmogenic properties of halothane.