title: 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 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.
authors.affiliation: 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
authors.forename: Alicia
authors.initials: A
authors.lastname: Mattiazzi
authors.forename: Leticia
authors.initials: L
authors.lastname: Vittone
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mundiña-Weilenmann
mesh_terms: 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
chemical_list: D015220:Calcium Channels; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium