Age-related regulation of excitation–contraction coupling in rat heart

Abstract

Hearts from subjects with different ages have different Ca(2+) signaling. Release of Ca(2+) from intracellular stores in response to an action potential initiates cardiac contraction. Both depolarization-stimulated and spontaneous Ca(2+) releases, Ca(2+) transients and Ca(2+) sparks, demonstrate the main events of excitation-contraction coupling (ECC). Global increase in free Ca(2+) concentration ([Ca(2+)]( i )) consists of summation of Ca(2+) release events in cardiomyocytes. Since the Ca(2+) flux induced by Ca(2+) sparks reports a summation of ryanodine-sensitive Ca(2+) release channels (RyR2s)'s behavior in a spark cluster, evaluation of the properties of Ca(2+) sparks and Ca(2+) transients may provide insight into the role of RyR2s on altered heart function between 3-month-old (young adult) and 6-month-old (mature adult) rats. Basal [Ca(2+)]( i ) and Ca(2+) sparks frequency were significantly higher in mature adult rats compared to those of young adults. Moreover, amplitudes of Ca(2+) sparks and Ca(2+) transients were significantly smaller in mature adults than those of young adults with longer time courses. A smaller L-type Ca(2+) current density and decreased SR Ca(2+) load was observed in mature adult rats. In addition, RyR2s were markedly hyperphosphorylated, and phosphorylation levels of PKA and CaMKII were higher in heart from mature adults compared to those of young adults, whereas their SERCA protein levels were similar. Our data demonstrate that hearts from rats with different ages have different Ca(2+) signaling including hyperphosphorylation of RyR2s and higher basal [Ca(2+)]( i ) together with increased oxidized protein-thiols in mature adult rats compared to those of young adults, which play important roles in ECC. Finally, we report that ECC efficiency changes with age during maturation, partially related with an increased cellular oxidation level leading to reduced free protein-thiols in cardiomyocytes.