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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

Strathprints serves world leading Open Access research by the University of Strathclyde, including research by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), where research centres such as the Industrial Biotechnology Innovation Centre (IBioIC), the Cancer Research UK Formulation Unit, SeaBioTech and the Centre for Biophotonics are based.

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Interaction of calcium/calmodulin-dependent protein kinase IIδC with sorcin indirectly modulates ryanodine receptor function in cardiac myocytes

Currie, S. and Anthony, D.F. and Beattie, J. and Paul, A. (2007) Interaction of calcium/calmodulin-dependent protein kinase IIδC with sorcin indirectly modulates ryanodine receptor function in cardiac myocytes. Journal of Molecular and Cellular Cardiology, 43 (4). pp. 492-503. ISSN 0022-2828

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Abstract

Calcium/calmodulin dependent protein kinase II delta C (CaMKIIδC) and the EF-hand Ca2+-binding protein, sorcin have both been shown to regulate the excitation-contraction coupling process. This study explores the possibility that these two proteins interact directly and, as a result of this interaction, modulate cardiac calcium handling. Two independent methods (surface plasmon resonance (SPR) and overlay assays) were used to determine whether CaMKIIδC and sorcin interacted in a direct manner. The nature of this interaction was explored by (i) examining the effects of sorcin on CaMKIIδC activity using a selective kinase assay and (ii) studying whether sorcin was a substrate for CaMKIIδC using autoradiography. Ryanodine binding assays on mouse ventricular cardiomyocytes were used to determine specific functional effects of this interaction. SPR studies suggested that sorcin interacts with CaMKIIδC in a concentration-dependent manner. This interaction occurs in the presence of Ca2+ and in the presence or absence of calmodulin (CaM). Overlay assays confirmed the existence of this interaction. Further experiments suggested that this interaction is reciprocal. Firstly, sorcin significantly inhibited both recombinant and native CaMKIIδC activity to similar extents. Secondly, sorcin was phosphorylated by CaMKIIδC. Thirdly, sorcin inhibition of CaMKII activity occurred under conditions where sorcin remained dephosphorylated. Functionally, CaMKIIδC-mediated phosphorylation of sorcin served to abolish the inhibitory effect of sorcin on ryanodine receptor (RyR2) open probability (Po). Since both proteins are capable of directly modulating RyR2 activity, this interaction may serve as an additional or alternative indirect route by which both proteins can regulate RyR2 opening status in cardiac myocytes.