Effect of bupivacaine on ATP-dependent potassium channels in rat cardiomyocytes

Bupivacaine induces fatal arrhythmia when accidentally injected i.v. or overdosed, whereas lidocaine is used as an anti-arrhythmic agent. We have suggested recently that the antiarrhythmic effect of lidocaine may be explained by suppression of ATP-sensitive potassium (K-ATP) channels. Therefore, it could be argued that different sensitivities of K-ATP channels to both drugs could be a reason for their different arrhythmic and anti-arrhythmic properties. In this study, we have investigated the direct action of bupivacaine on K-ATP channels in cardiomyocytes. The effects of bupivacaine on the cardiac K-ATP channel were investigated using the patch-clamp technique on enzymatically dissociated cardiomyocytes of adult rats. Bupivacaine was applied to the outer side of excised membrane patches using a multiple-barrel perfusion system. Concentration-response curves indicated that bupivacaine blocked the mean current of the K-ATP channels at a half-maximum inhibiting concentration (IC50) of 29 mu mol litre(-1), similar to that reported for lidocaine (43 mu mol litre(-1)). Binding of bupivacaine influenced the gating of this channel, but did not reduce the conductance of the open channel. Bupivacaine and lidocaine were equipotent in blocking K-ATP channels. However, because of its excessive block of the sodium channel in the inactivated state, block of K-ATP channels by bupivacaine will only enhance its cardiotoxicity.