CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Role of Ito defining Ca2+ dynamics on intact mouse hearts
Autor/es:
FELICE, JUAN IGNACIO; MEDEI, EMILIANO; LÓPEZ ALARCÓN, MICAELA; ESCOBAR, ARIEL L
Lugar:
Ciudad Autónoma de Buenos Aires
Reunión:
Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017
Resumen:
During a physiological cardiac cycle, an influx of Ca2+through L-type Ca2+ channels is responsible for triggering Ca2+release from the sarcoplasmic reticulum (SR). Although in most of vertebrates thisinflux occurs during the plateau phase of the ventricular action potential(ph2) in murine models this happens on the early repolarizing phase 1 (ph1).The aim of this work is to asses if changes in the open probability of K+channels defining ph1 (Ito) can modulate both Ca2+ currents and Ca2+release from the SR during the ventricular AP. A combination of pulsed localfield microscopy (PLFFM), loose patch photolysis (LPP) and mathematicalmodeling was used to test the hypothesis that a decrease in Ito will enhance Ca2+influx and SR Ca2+ release. A mouse myocyte mathematical model used tovalidate our working hypothesis, predicted that a decrease in the ph1repolarization rate promote an increase in the amplitude of the L-type Ca2+current, the SR Ca2+ load and in the gain of the Ca2+inducedCa2+ release process. This theoretical prediction was experimentallyevaluated using LPP. Indeed, increasing concentrations of 4 aminopyridine(4-AP) slowed down ph1 repolarization and increased Ca2+ influxthrough L-type Ca2+ channels. Furthermore, the activation of Itowith NS-5806 reduced the amplitude of nifedipine-sensitive Ca2+ currents.In addition, simultaneous recordings of Ca2+ transients and APs byPLFFM showed that a reduction in the ph1 repolarization rate produced anincrease in the amplitude of Ca2+ transients and that an increase inthe repolarization rate promoted by NS-5806 led to a reduction of SR Ca2+release. Finally, 4-AP effect on AP ph1 repolarization was significantlysmaller when the L-type Ca2+ current was partially blocked withnifedipine. This indicates that not only ph1 repolarization rate regulatescardiac contractility, but also that the rate of repolarization is defined bythe competition between an outward K+ current and an inward Ca2+current.