The repolarization during phase-1 defines Ca2+ transients and contractility in perfused mouse heartsAuthor(s): Emiliano Medei, Maedeh Bazmi, Ariel L Escobar
In perfused hearts, Ca2+ influx through L-type Ca2+ channels triggers Ca2+ release from the sarcoplasmic reticulum. In nearly all mammals, the inflow which activates the sarcoplasmic reticulum Ca2+ release occurs during phase 2 of the action potential. Interestingly, in murine models, the triggering event occurs during phase 1 of the action potential. The objective of this review is to determine how much Ca2+ influx occurs during phase 1. Moreover, we want to determine how much Ca2+ gets into the myocytes when Kv4.3 is blocked with 4-aminopyridine (4-AP). Moreover, we will evaluate changes in the open probability of Kv 4.3 following blockage via 4-aminopyridine (4-AP). To test whether a decrease in a transient K+ current (Ito) will enhance Ca2+ influx across the plasma membrane and increase the amplitude of Ca2+ transients, pulsed local-field fluorescence microscopy, recordings using sharp microelectrodes, measurements of the developed pressure, and loose-patch photolysis were utilized. Furthermore, some experiments were performed using loose patch photolysis to evaluate the amplitude of the Ca2+ in intact beating hearts. Interestingly, 4-AP increased not only the time required for AP to reach 30% repolarization but also the amplitude of Ca2+ transients in the epicardium in comparison to the endocardium. Furthermore, the activation of Ito with N-[3,5-Bis(trifluoromethyl)phenyl]-N’-[2,4- dibromo-6-(2H-tetrazol-5-yl)phenyl]urea (NS5806) resulted in a reduction of Ca2+ current amplitude, which led to a reduction of the amplitude of Ca2+ transients.