TY - JOUR T1 - Simulation analysis of intracellular Na+ and Cl- homeostasis during beta 1-adrenergic stimulation of cardiac myocyte. AU - Kuzumoto,Masanori, AU - Takeuchi,Ayako, AU - Nakai,Hiroyuki, AU - Oka,Chiaki, AU - Noma,Akinori, AU - Matsuoka,Satoshi, Y1 - 2007/08/01/ PY - 2007/9/11/pubmed PY - 2008/5/31/medline PY - 2007/9/11/entrez SP - 171 EP - 86 JF - Progress in biophysics and molecular biology JO - Prog Biophys Mol Biol VL - 96 IS - 1-3 N2 - To quantitatively understand intracellular Na+ and Cl- homeostasis as well as roles of Na+/K+ pump and cystic fibrosis transmembrane conductance regulator Cl- channel (ICFTR) during the beta1-adrenergic stimulation in cardiac myocyte, we constructed a computer model of beta1-adrenergic signaling and implemented it into an excitation-contraction coupling model of the guinea-pig ventricular cell, which can reproduce membrane excitation, intracellular ion changes (Na+, K+, Ca2+ and Cl-), contraction, cell volume, and oxidative phosphorylation. An application of isoproterenol to the model cell resulted in the shortening of action potential duration (APD) after a transient prolongation, the increases in both Ca2+ transient and cell shortening, and the decreases in both Cl- concentration and cell volume. These results are consistent with experimental data. Increasing the density of ICFTR shortened APD and augmented the peak amplitudes of the L-type Ca2+ current (ICaL) and the Ca2+ transient during the beta1-adrenergic stimulation. This indirect inotropic effect was elucidated by the increase in the driving force of ICaL via a decrease in plateau potential. Our model reproduced the experimental data demonstrating the decrease in intracellular Na+ during the beta-adrenergic stimulation at 0 or 0.5 Hz electrical stimulation. The decrease is attributable to the increase in Na+ affinity of Na+/K+ pump by protein kinase A. However it was predicted that Na+increases at higher beating rate because of larger Na+ influx through forward Na+/Ca2+ exchange. It was demonstrated that dynamic changes in Na+ and Cl- fluxes remarkably affect the inotropic action of isoproterenol in the ventricular myocytes. SN - 0079-6107 UR - https://www.unboundmedicine.com/medline/citation/17826821/Simulation_analysis_of_intracellular_Na+_and_Cl__homeostasis_during_beta_1_adrenergic_stimulation_of_cardiac_myocyte_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0079-6107(07)00049-1 DB - PRIME DP - Unbound Medicine ER -