Vol. 281, Issue 2, 826-833, 1997

Effects of Cadmium and Nisoldipine on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes¹

Pascal Daleau² , Majed Khalifa³ and Jacques Turgeon⁴

Quebec Heart Institute, Laval Hospital, Faculty of Medicine, Department of Pharmacology, Laval University (P.D.) and School of Pharmacy, Laval University (M.K., J.T.), Ste-Foy, P.Q., Canada, G1V 4G5

Block of the slow inward calcium current (I_si) during assessment of the delayed rectifier potassium current (I_K) of cardiac ventricular myocytes is commonly achieved by use of either inorganic compounds such as cadmium or dihydropyridine derivatives such as nisoldipine. Effects of these two I_si blockers on I_K characteristics of guinea pig ventricular myocytes were compared in this study. Currents were measured in the whole cell configuration of the patch-clamp technique and I_K tail amplitudes were measured at 40 mV after depolarizations to various test potentials (voltage steps, 20 to +50 mV) for either 250 (I_K250), 450 (I_K450) or 5000 (I_K5000) msec. Activating and tail currents measured in the presence of cadmium were of greater amplitudes when voltage steps were more positive than 0 mV but were of smaller amplitudes at V_test  0 mV compared to currents measured in the presence of nisoldipine or Tyrode solution. In the presence of the rapid component of the delayed rectifier E-4031, a blocker of cadmium increased I_Ks amplitude during high voltage tests and caused a positive shift in the voltage dependence of I_Ks activation at low depolarizing potentials. In contrast, no effect on I_K was observed when nisoldipine was added to Tyrode solution. In conclusion, results obtained in this study suggest that cadmium depresses and/or shifts the activation curve of the rapid component and increases and positively shifts the slow component of I_K in guinea pig ventricular myocytes. These observations lead us to propose that nisoldipine may be a better tool to inhibit long lasting inward calcium current during assessment of I_K.