Dynamic Kv4.3-CaMKII unit in heart: an intrinsic negative regulator for CaMKII activation.

ABSTRACT:

Aims

Reduction of transient outward current (I(to)) and excessive activation of Ca(2+)/Calmodulin-dependent kinase II (CaMKII) are general features of ventricular myocytes in heart failure. We hypothesize that alterations of I(to) directly regulate CaMKII activation in cardiomyocytes.

Methods and results

A dynamic coupling of I(to) channel subunit Kv4.3 and inactive CaMKII was discovered in cardiomyocytes with the membrane predominant distribution by co-immunoprecipitation and fluorescence resonance energy transfer techniques. CaMKII dissociation from Kv4.3-CaMKII units caused a significant increase in CaMKII autophosphorylation and L-type calcium current (I(Ca)) facilitation. I(Ca) facilitation was blunted by the compartmental Ca²(+) chelator BAPTA but unaffected by bulk Ca

SUBMITTER: Keskanokwong T 

PROVIDER: S-EPMC3031792 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature