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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences physical, and engineering sciences, 2006-05, Vol.364 (1842), p.1223-1243
Hauptverfasser: Leem, Chae Hun, Kim, Won Tae, Ha, Jeong Mi, Lee, Yoon Jin, Seong, Hyeon Chan, Choe, Han, Jang, Yeon Jin, Youm, Jae Boum, Earm, Yung E
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:1364-503X
1471-2962
DOI:10.1098/rsta.2006.1766