On the Nature of the L-type Ca2+ Current Inactivation in Rat Ventricular Cardiomyocytes

M. Sampedro-Castañeda; J. Alvarez-Collazo; L. Galán-Martínez; A. I. López-Medina; G. Vassort; J. L. Álvarez

M. Sampedro-Castañeda Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba.
J. Alvarez-Collazo Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba.
L. Galán-Martínez Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba.
A. I. López-Medina Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba.
G. Vassort Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba.
J. L. Álvarez Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba.

Abstract

Facilitation of cardiac L-type Ca²⁺ current (I_CaL) by high stimulation rates or by depolarizing prepulses is characterized by an increase in the fast inactivation time constant (t_fast) of I_CaL. To explain this phenomenon, mechanisms related to calcium-dependent inactivation (CDI) have been considered. Here we studied in more
detail the mechanism of I_CaL facilitation by depolarizing prepulses using isolated rat ventricular cardiomyocytes. Increases in f ast at a test pulse to 0 mV by low voltage (not activating I_CaL) prepulses were associated with hyperpolarizing shifts in I_CaL kinetics. Experimental conditions aimed to decrease CDI, by blocking the Ca²⁺ release from or its reload to the sarcoplasmic reticulum, did not abolish the increase in f ast by prepulses. Our results suggest that this kind of I_CaL facilitation is also associated to a strong voltage-dependent mechanism. A model is proposed in which depolarizing prepulses allow the Ca²⁺ channel to dwell longer times in the open state.