Effects of cadmium and nisoldipine on the delayed rectifier potassium current in guinea pig ventricular myocytes.
Block of the slow inward calcium current (Isi) during assessment of the delayed rectifier potassium current (IK) 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 Isi blockers on IK 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 IK tail amplitudes were measured at -40 mV after depolarizations to various test potentials (voltage steps, -20 to +50 mV) for either 250 (IK250), 450 (IK450) or 5000 (IK5000) 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 Vtest < or = 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 IKs amplitude during high voltage tests and caused a positive shift in the voltage dependence of IKs activation at low depolarizing potentials. In contrast, no effect on IK 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 IK 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 IK.
Daleau
P
P
Quebec Heart Institute, Laval Hospital, Faculty of Medicine, Department of Pharmacology, Laval University, Ste-Foy, Canada.
Khalifa
M
M
Turgeon
J
J
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015737:Nisoldipine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D016276:Ventricular Function
D002121:Calcium Channel Blockers; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D002104:Cadmium; D015737:Nisoldipine