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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Mattiazzi A,Vittone L,Mundiña-Weilenmann C

doi

10.1016/j.cardiores.2006.12.002

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

648-56

issue

4

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(06)00565-7

journal_volume

73

pub_type

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