CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Transient Outward K Current Defines Ca Dynamics on Intact Mouse Hearts
Autor/es:
FELICE, JUAN IGNACIO; ESCOBAR, ARIEL L; LÓPEZ ALARCÓN, MICAELA; MEDEI, EMILIANO
Lugar:
San Francisco
Reunión:
Encuentro; 62nd Annual Meeting - Biophysical Society; 2018
Institución organizadora:
The Biophysical Society
Resumen:
Inthe heart, a Ca2+ influx through L-type Ca2+ channelstriggers Ca2+ release from the sarcoplasmic reticulum (SR). Invertebrates, this influx occurs during the ventricular action potential plateauphase (ph2). However, in murine models, this happens on the early repolarizingphase 1 (ph1). The aim of this work is to assess if changes in the openprobability of K+ channels defining ph1 (Ito) can modulate both Ca2+currents and Ca2+ release from the SR during the ventricular AP.Pulsed local field microscopy (PLFFM), loose patch photolysis (LPP) andmathematical modeling were used to test the hypothesis that a decrease in Itowill enhance Ca2+ influx and SR Ca2+ release. A mousemyocyte mathematical model predicted that a decrease in the ph1 repolarizationrate promotes an increase in the amplitude of the L-type Ca2+current, the SR Ca2+ load and in the gain of the Ca2+induced Ca2+ release process. This theoretical prediction wasexperimentally evaluated using LPP. Indeed, increasing concentrations of 4aminopyridines (4-AP) slowed down ph1 repolarization and increased Ca2+influx through L-type Ca2+ channels. Furthermore, Ito activationwith NS-5806 reduced the amplitude of Ca2+ currents. In addition,simultaneous recordings of Ca2+ transients and APs by PLFFM showedthat a reduction in the ph1 repolarization rate produced an increase in theamplitude of Ca2+ transients and that an increase in therepolarization rate promoted by NS-5806 led to a reduction of SR Ca2+release. Finally, the 4-AP effect on AP ph1 was significantly smaller when theL-type Ca2+ current was partially blocked with nifedipine. Thisindicates that not only ph1 repolarization rate regulates cardiaccontractility, but also that the rate of repolarization is defined by thecompetition between an outward K+ current and an inward Ca2+current.