Inhibition of cardiac potassium currents by pentobarbital

Abstract.

The inhibitory effects of the anesthetic barbiturate pentobarbital on the slow (I _Ks) and fast component (I _Kr) of cardiac delayed rectifier potassium currents (I _K) and on the inward rectifier potassium currents (I _K1) were examined in Xenopus oocytes expressing the human minK, human ether-á-go-go related gene (HERG) and guinea pig Kir2.2, respectively. Block of native I _K (I _Ks and I _Kr) and inward rectifier potassium current (I _K1) by pentobarbital was examined in guinea pig ventricular myocytes.

In oocytes using the two electrode voltage clamp technique potassium currents of hminK-, HERG- and Kir2.2-expressing oocytes were inhibited by pentobarbital with IC₅₀ values of 0.20, 1.58 and 0.54 mM, respectively. I _Ks block was time- and voltage-independent and had no influence on activation at positive voltages although it shifted voltage-dependent activation to more positive voltages. Pentobarbital-induced HERG inhibition was not dependent on voltage but influenced the deactivation kinetics and shifted half-maximal activation to more negative voltages. In guinea pig cardiomyocytes, using the patch clamp technique, I _Ks and I _Kr were inhibited by pentobarbital with IC₅₀ values of 0.18 mM and 2.75 mM, respectively. I _Kr deactivation and I _Ks activation kinetics were only slightly influenced by pentobarbital, if at all. Block of I _K1 was weakly voltage-dependent with IC₅₀ values of 0.26 mM (–40 mV) and 0.91 mM (–120 mV). The data show that pentobarbital suppresses both cloned (I _K, I _Kir2.2) and native (I _K, I _K1) cardiac potassium currents with the highest affinity for I _Ks.