S100A1 increases the gain of excitation-contraction coupling in isolated rabbit ventricular cardiomyocytes.
The effect of S100A1 protein on cardiac excitation-contraction (E-C) coupling was studied using recombinant human S100A1 protein (0.01-10 microM) introduced into single rabbit ventricular cardiomyocytes via a patch pipette. Voltage clamp experiments (20 degrees C) indicated that 0.1 microM S100A1 increased Ca(2+) transient amplitude by approximately 41% but higher or lower S100A1 concentrations had no significant effect. L-type Ca(2+) current amplitude or Ca(2+) efflux rates via the Na(+)/Ca(2+) exchanger (NCX) were unaffected. The rate of Ca(2+) uptake associated with the SR Ca(2+)-ATPase (SERCA2a) was increased by approximately 22% with 0.1 microM S100A1, but not at other S100A1 concentrations. Based on the intracellular Ca(2+) and I(NCX) signals in response to 10 mM caffeine, no significant change in SR Ca(2+) content was observed with S100A1 (0.01-10 microM). Therefore, 0.1 microM S100A1 appeared to increase the fractional Ca(2+) release from the SR. This result was confirmed by measurements of Ca(2+) transient amplitude at a range of SR Ca(2+) contents. The hyperbolic relationship between these two parameters was shifted to the left by 0.1 microM S100A1. [(3)H]-ryanodine binding studies indicated that S100A1 increased ryanodine receptor (RyR) activity at 0.1 and 0.3 microM Ca(2). As with the effects on E-C coupling, 0.1 microM S100A1 produced the largest effect. Co-immunoprecipitation studies on a range of Ca(2+)-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 Ca(2+) transient amplitude without significantly affecting the SR Ca(2+) content.
Kettlewell
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Institute of Biomedical and Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Most
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Currie
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Koch
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Smith
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D009418:S100 Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D002135:Calcium-Binding Proteins; D011994:Recombinant Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D009418:S100 Proteins; C110294:S100A1 protein; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium