Kettlewell, S., Most, P., Currie, S., Koch, W. and Smith, G. (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. (doi: 10.1016/j.yjmcc.2005.06.018)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Smith, Professor Godfrey and Kettlewell, Dr Sarah |
| Authors: | Kettlewell, S., Most, P., Currie, S., Koch, W., and Smith, G. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences |
| Journal Name: | Journal of Molecular and Cellular Cardiology |
| Publisher: | Elsevier |
| ISSN: | 0022-2828 |
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