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  • Title: Simulation of Ca2+-activated Cl- current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca2+ dynamics.
    Author: Leem CH, Kim WT, Ha JM, Lee YJ, Seong HC, Choe H, Jang YJ, Youm JB, Earm YE.
    Journal: Philos Trans A Math Phys Eng Sci; 2006 May 15; 364(1842):1223-43. PubMed ID: 16608705.
    Abstract:
    In recent studies, we recorded transiently activated outward currents by the application of three-step voltage pulses to induce a reverse mode of Na+-Ca2+ exchange (NCX). We found that these currents were mediated by a Ca2+-activated Cl- current. Based on the recent reports describing the atrial Ca2+ transients, the Ca2+ 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 Ca2+-activated Cl- current may reflect the subsarcolemmal Ca2+ dynamics. We tried to predict the subsarcolemmal Ca2+ 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 Ca2+ buffers, were obtained from the literature. In the simulation, we incorporated the NCX, the L-type Ca2+ channel, the rapid activating outward rectifier K+ channel, the Na+-K+ pump, the SR Ca2+-pump, the ryanodine receptor, the Ca2+-activated Cl- channel and the dynamics of Na+, K+, Ca2+ and Cl-. In these conditions, we could successfully reconstruct the Ca2+-activated Cl- currents. The simulation allowed estimation of the Ca2+ dynamics of each compartment and the distribution of the Ca2+-activated Cl- channel and the NCX in the sarcolemma on the junctional or subsarcolemmal space.
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