Effects of ketamine on voltage-dependent calcium currents and membrane potentials in single bullfrog atrial cells

Purpose. This study was undertaken to assess the effect of ketamine on L-type calcium channel current (I_Ca) and membrane action potential in the bullfrog single atrial myocyte. Methods. Bullfrog single atrial myocytes were prepared by enzymatic dispersion. Whole-cell voltage-clamp technique and current clamp technique were used to monitor I_Ca, membrane resting potential, and action potential. Results. Ketamine (10^-5-10^-3 M) showed dose-dependent inhibition of I_Ca in a reversible manner. The 50% inhibitory concentration (IC₅₀) of ketamine on I_Ca was estimated to be 0.92 × 10^-5 M. Use-dependent block of I_Ca was not observed. The resting membrane potential was depolarized at a high concentration (10^-4 M) of ketamine. Reduction of the plateau phase and prolonged duration of the action potential were observed in the presence of a high concentration of ketamine (10^-4 M). Conclusion. Ketamine has an inhibitory effect on I_Ca in the bullfrog single atrial myocyte, and a high dose (10^-4 M) of ketamine prolonges the duration of the action potential. The mechanism of inhibition of I_Ca seems to be a direct effect on the L-type calcium channel, not like an open channel blocker.