Simulation of Ca 2+ -activated Cl − current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca 2+ dynamics

In recent studies, we recorded transiently activated outward currents by the application of three-step voltage pulses to induce a reverse mode of Na + –Ca 2+ exchange (NCX). We found that these currents were mediated by a Ca 2+ -activated Cl − current. Based on the recent reports describing the atrial Ca 2+ transients, the Ca 2+ transient at the subsarcolemmal space was initiated and then diffused into the cytosolic space. Because the myocardium in the pulmonary vein is an extension of the atrium, the Ca 2+ -activated Cl − current may reflect the subsarcolemmal Ca 2+ dynamics. We tried to predict the subsarcolemmal Ca 2+ dynamics by simulating these current traces. According to recent reports on the geometry of atrial myocytes, we assumed that there were three compartments of sarcoplasmic reticulum (SR): a network SR, a junctional SR and a central SR. Based on these structures, we also divided the cytosolic space into three compartments: the junctional, subsarcolemmal and cytosolic spaces. Geometry information and cellular capacitance suggested that there were essentially no T-tubules in these cells. The basic physical data, such as the compartmental volumes, the diffusion coefficients and the stability coefficients of the Ca 2+ buffers, were obtained from the literature. In the simulation, we incorporated the NCX, the L-type Ca 2+ channel, the rapid activating outward rectifier K + channel, the Na + –K + pump, the SR Ca 2+ -pump, the ryanodine receptor, the Ca 2+ -activated Cl − channel and the dynamics of Na + , K + , Ca 2+ and Cl − . In these conditions, we could successfully reconstruct the Ca 2+ -activated Cl − currents. The simulation allowed estimation of the Ca 2+ dynamics of each compartment and the distribution of the Ca 2+ -activated Cl − channel and the NCX in the sarcolemma on the junctional or subsarcolemmal space.