Ca2+/calmodulin-dependent protein kinase: A key component in the contractile recovery from acidosis

Abstract

Intracellular acidosis exerts substantial effects on the contractile performance of the heart. Soon after the onset of acidosis, contractility diminishes, largely due to a decrease in myofilament Ca2+ responsiveness. This decrease in contractility is followed by a progressive recovery that occurs despite the persistent acidosis. This recovery is the result of different mechanisms that converge to increase diastolic Ca2+ levels and Ca2+ transient amplitude. Recent experimental evidence indicates that activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) is an essential step in the sequence of events that increases the Ca2+ transient amplitude and produces contractile recovery. CaMKII may act as an amplifier, providing compensatory pathways to offset the inhibitory effects of acidosis on many of the Ca2+ handling proteins. CaMKII-induced phosphorylation of the SERCA2a regulatory protein phospholamban (PLN) has the potential to promote an increase in sarcoplasmic reticulum (SR) Ca2+ uptake and SR Ca2+ load, and is a likely candidate to mediate the mechanical recovery from acidosis. In addition, CaMKII-dependent phosphorylation of proteins other than PLN may also contribute to this recovery.