Modelling sarcoplasmic reticulum calcium ATPase and its regulation in cardiac myocytes BY JUSSI T. KOIVUMA ¨ KI 1,2 ,JOUNI TAKALO 1,2 ,TOPI KORHONEN 2,3 , PASI TAVI 2,3 AND MATTI WECKSTRO ¨ M 1,2, * 1 Division of Biophysics, Department of Physical Sciences, 2 Biocenter Oulu, and 3 Department of Physiology, Institute of Biomedicine, University of Oulu, 90014 Oulu, Finland When developing large-scale mathematical models of physiology, some reduction in complexity is necessarily required to maintain computational efficiency. A prime example of such an intricate cell is the cardiac myocyte. For the predictive power of the cardiomyocyte models, it is vital to accurately describe the calcium transport mechanisms, since they essentially link the electrical activation to contractility. The removal of calcium from the cytoplasm takes place mainly by the Na C /Ca 2C exchanger, and the sarcoplasmic reticulum Ca 2C ATPase (SERCA). In the present study, we review the properties of SERCA, its frequency-dependent and b-adrenergic regulation, and the approaches of mathematical modelling that have been used to investigate its function. Furthermore, we present novel theoretical considerations that might prove useful for the elucidation of the role of SERCA in cardiac function, achieving a reduction in model complexity, but at the same time retaining the central aspects of its function. Our results indicate that to faithfully predict the physiological properties of SERCA, we should take into account the calcium-buffering effect and reversible function of the pump. This ‘uncomplicated’ modelling approach could be useful to other similar transport mechanisms as well. Keywords: heart; calcium; sarcoplasmic reticulum Ca 2D ATPase; mathematical modelling 1. Calcium transport in cardiomyocytes: role of sarcoplasmic reticulum Ca 2D ATPase In cardiac myocytes, the contraction force produced by the contractile apparatus is directly (albeit not linearly) related to the momentary calcium concentration in the cytoplasm. The continuous contraction–relaxation cycle, characteristic of heart function, is created by oscillation-like increases and decreases in calcium concentration, the Ca 2C transients. These arise from a complex chain of events, collectively known as excitation–contraction (E–C) coupling, which is paced by membrane action potentials (APs). During the cycle, Ca 2C flows into the Phil. Trans. R. Soc. A (2009) 367, 2181–2202 doi:10.1098/rsta.2008.0304 One contribution of 15 to a Theme Issue ‘The virtual physiological human: tools and applications II’. * Author and address for correspondence: Department of Physical Sciences, University of Oulu, PO Box 3000, 90014 Oulu, Finland (matti.weckstrom@oulu.fi). 2181 This journal is q 2009 The Royal Society on January 15, 2016 http://rsta.royalsocietypublishing.org/ Downloaded from