S100A1 increases the gain of excitation-contraction coupling in isolated rabbit ventricular cardiomyocytes

Kettlewell, S. and Most, P. and Currie, S. and Koch, W.J. and Smith, G.L. (2005) S100A1 increases the gain of excitation-contraction coupling in isolated rabbit ventricular cardiomyocytes. Journal of Molecular and Cellular Cardiology, 39 (6). pp. 900-910. ISSN 0022-2828 (http://dx.doi.org/10.1016/j.yjmcc.2005.06.018)

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The effect of S100A1 protein on cardiac excitation-contraction (E-C) coupling was studied using recombinant human S100A1 protein (0.01-10 mu M) introduced into single rabbit ventricular cardiomyocytes via a patch pipette. Voltage clamp experiments (20 degrees C) indicated that 0.1 mu M S100A1 increased Ca2+ transient amplitude by similar to 41% but higher or lower S100A1 concentrations had no significant effect. L-type Ca2+ current amplitude or Ca2+ efflux rates via the Na+/Ca2+ exchanger (NCX) were unaffected. The rate of Ca2+ uptake associated with the SR Ca2+-ATPase (SERCA2a) was increased by similar to 22% with 0.1 mu M S100A1, but not at other S100A1 concentrations. Based on the intracellular Ca2+ and I-NXC signals in response to 10 mM caffeine, no significant change in SR Ca2+ content was observed with S100A1 (0.01-10 mu M). Therefore, 0.1 mu M S100A1 appeared to increase the fractional Ca2+ release from the SR. This result was confirmed by measurements of Ca2+ transient amplitude at a range of SR Ca2+ contents. The hyperbolic relationship between these two parameters was shifted to the left by 0.1 mu M S100A1. [H-3]-ryanodine binding studies indicated that S100A1 increased ryanodine receptor (RyR) activity at 0.1 and 0.3 mu M Ca-2. As with the effects on E-C coupling, 0.1 mu M S100A1 produced the largest effect. Co-immunoprecipitation studies on a range of Ca2+- handling proteins support the selective interaction of S100A1 on SERCA2a and RyR. In summary, S100A1 had a stimulatory action on RyR2 and SERCA2a in rabbit cardiomyocytes. Under the conditions of this study, the net effect of this dual action is to enhance the Ca2+ transient amplitude without significantly affecting the SR Ca2+ content.