In: General Physiology and Biophysics, vol. 28, no. 4
Konstantin Gusev - Gabriele Ackermann - Claus Heizmann - Ernst Niggli
Details:
Year, pages: 2009, 371 - 383
About article:
S100A1 is a Ca2+-binding protein expressed at high levels in the myocardium. It is thought to modulate the Ca2+ sensitivity of the sarcoplasmic reticulum (SR) Ca2+ release channels (ryanodine receptors or RyRs) and its expression has been shown to be down regulated in various heart diseases. In this study we used S100A1 knock-out (KO) mice to investigate the consequences of chronic S100A1 deficiency on Ca2+ cycling in ventricular cardiomyocytes. Confocal Ca2+ imaging showed that field-stimulated KO myocytes had near normal Ca2+ signaling under control conditions but a blunted response to β-adrenergic stimulation with 1 µmol/l isoproterenol (ISO). Voltage-clamp experiments revealed that S100A1-deficient cardiomyocytes have elevated ICa under basal conditions. This larger Ca2+ influx was accompanied by augmented Ca2+ transients and elevated SR Ca2+ content, without changes in macroscopic excitation-contraction coupling gain, which suggests impaired fractional Ca2+ release. Exposure of KO and WT cells to ISO led to similar maximal ICa . Thus, the stimulation of the ICa was less pronounced in KO cardiomyocytes, suggesting that changes in basal ICa could underlie the reduced β-adrenergic response. Taken together, our findings indicate that chronic absence of S100A1 results in enhanced L-type Ca2+ channel activity combined with a blunted SR Ca2+ release amplification. These findings may have implications in a variety of cardiac pathologies where abnormal RyR Ca2+ sensitivity or reduced S100A1 levels have been described.
How to cite:
ISO 690:
Gusev, K., Ackermann, G., Heizmann, C., Niggli, E. 2009. Ca2+ signaling in mouse cardiomyocytes with ablated S100A1 protein. In General Physiology and Biophysics, vol. 28, no.4, pp. 371-383. 0231-5882.
APA:
Gusev, K., Ackermann, G., Heizmann, C., Niggli, E. (2009). Ca2+ signaling in mouse cardiomyocytes with ablated S100A1 protein. General Physiology and Biophysics, 28(4), 371-383. 0231-5882.