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.