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

MATTIAZZI A; VITTONE L; MUNDIÑA-WEILENMANN C

CARDIOVASCULAR RESEARCH

European Society of Cardiology

Año: 2007 vol. 73 p. 648 - 656

0008-6363

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 Ca(2+) 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 Ca(2+) levels and Ca(2+) transient amplitude. Recent experimental evidence indicates that activation of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an essential step in the sequence of events that increases the Ca(2+) 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 Ca(2+) handling proteins. CaMKII-induced phosphorylation of the SERCA2a regulatory protein phospholamban (PLN) has the potential to promote an increase in sarcoplasmic reticulum (SR) Ca(2+) uptake and SR Ca(2+) 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.