Simulation of Ca2+-activated Cl- current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca2+ 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+-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.
Leem
Chae Hun
CH
Department of Physiology, University of Ulsan College of Medicine, 388-1 Poongnap-Dong Songpa-Ku, Seoul 138-736, South Korea. leemch@amc.seoul.kr
Kim
Won Tae
WT
Ha
Jeong Mi
JM
Lee
Yoon Jin
YJ
Seong
Hyeon Chan
HC
Choe
Han
H
Jang
Yeon Jin
YJ
Youm
Jae Boum
JB
Earm
Yung E
YE
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D002713:Chlorine / Q000378:metabolism*; D003198:Computer Simulation; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology*; D011667:Pulmonary Veins / Q000166:cytology / Q000502:physiology*; D011817:Rabbits; D012508:Sarcolemma / Q000502:physiology*
D002713:Chlorine; D002118:Calcium