|Title||Rate-Dependent Regulation of Sarcoplasmic Reticulum Ca2+ ATPase in Human Atrial Myocytes|
|Afilliation||Center for Biomedical Computing (SFF), Scientific Computing, Scientific Computing|
|Project(s)||Center for Biomedical Computing (SFF)|
|Year of Publication||2011|
Aims: In mammalian cardiac myocytes, one of the most important regulators of intracellular calcium dynamics is the sarcoplasmic reticulum (SR) calcium ATPase (SERCA), which affects excitation-contraction coupling both ”upstream” (action potential) and ”downstream” (contractility). Accumulating evidence from ventricular myocytes suggests an important role for calcium/ calmodulin dependent kinase (CaMK) II in this context (Maier and Bers 2007); however, in atrial myocytes relatively little data exists on the rate-dependent regulation of SERCA. Methods: Here, we implement CaMK-dependent regulation of SERCA into a recently developed mathematical model of human atrial myocyte (Koivumäki et al. 2011), to study the rate dependence of SERCA's contribution to intracellular calcium recirculation. Results: Results indicate that stimulation of SERCA function, at high heart rates, promotes a substantial increase in SR calcium content and cytosolic calcium transient amplitude. Also, faster pacing shifts the balance of NCX vs. SERCA in calcium removal from cytosol during diastole. Conclusion: We conclude that CaMK-mediated stimulation of SERCA function is an important modulator of excitation-contraction coupling and rate dependence of action potential duration in atrial myocytes. References: Koivum¨aki, J.T., Korhonen, T., Tavi, P. 2011. PLoS Comput Biol 7(1): e1001067. Maier, L.S., Bers, D.M. 2007 Cardiovasc Res 73, 631-640.