Ketamine On Guinea Pig, Rat Ventricular Myocytes Ion Channels

Objective: To study the effect of ketamine on L-type calcium current in ventricular myocytes of guinea pigs. Methods: Single ventricular myocytes of guinea pigs were obtained by enzymatic dissociation method. Whole-cell patch-clamp recording technique was used to record the changes of L-type calcium currents in guinea pigs ventricle myocytes treated by different concentrarion of ketamine. Results Ketamine dose-dependently blocked the I_Ca-L currents evoked by a voltage step from a holding potential of -40mV to +10mV with a mean IC50 value of 926.6uM. After the cell exposed to ketamine 100uM,the steady-state activation curve was not significantly affected; while the steady-state inactivation curve shifted to more negative potentials, V_1/2 decreased from (-14.77 ± 0.78 )mV to (-19.56 ±0.73) mV (P<0.05) ,the slope factor(k)was (6.17±0.43) mV and (5.94±0.32) mV (P>0.05) in control and drug-used cells respectively; ketamine slowed the rate of recovery from inactivation. Conclusion Ketamine can inhibit I_Ca-L of guinea pig ventricular myocytes in a concentration-dependent manner, which might explain its negative inotropic effect. Ketamine inhibits L-type Ca²⁺ channel in its inactivation status.