Tonic Block of the Sodium and Calcium Currents by Ketamine in Isolated Guinea Pig Ventricular Myocytes

Abstract

Effects of ketamine on the sodium (I_Na) and L-type calcium currents (I_Ca) were examined by using whole-cell patch clamp techniques in guinea pig single ventricular myocytes. The mode of action of ketamine was compared with those of quinidine, a sodium channel blocker, and verapamil, a calcium channel blocker. Ketamine (30-300 μM) inhibited both I_Na and I_Ca in a concentration-dependent manner. Quinidine (30 μM) and verapamil (0.1 μM) produced use-dependent depression of I_Na and I_Ca, respectively. The amplitude of I_Na elicited by the first depolarizing pulse after a long quiescent period was slightly decreased by quinidine. During a train of depolarizing pulse the current amplitude decreased gradually, and reached a steady state level in the quinidine-treated cells (use-dependent block, UDB). Verapamil produced a similar mode of inhibition of I_Ca, i.e., UDB. In contrast, ketamine produced significant decrease in I_Na and I_Ca elicited by the first depolarizing pulses and the decreases of both currents were not augmented during a train of depolarizing pulses. From these results, it can be concluded that ketamine produces tonic block of the cardiac sodium and calcium channels and the mode of inhibition is clearly different from UDB by quinidine and verapamil.