Ca2+/calmodulin-dependent protein kinase: a key component in the contractile recovery from acidosis.
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.
Mattiazzi
Alicia
A
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120. (1900) La Plata, Argentina. ramattia@atlas.med.unlp.edu.ar
Vittone
Leticia
L
Mundiña-Weilenmann
Cecilia
C
D000138:Acidosis; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015220:Calcium Channels; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium