Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC265
Simulation analysis of Ca2+-dependent inhibition dynamics of L-type Ca2+ current of pulmonary vein cardiomyocytes of rabbit
H. Baek1, W. Kim1, J. Kwon1, J. Lee1, H. Kim1, C. Leem1
1. Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea, Republic of.
Ca2+ dependent inactivation (CDI) of L-type Ca2+ current (ICaL) is well known phenomena. In a recent report, Ca2+ release from the sarcoplasmic reticulum (SR) greatly affected the inactivation kinetics of L-type Ca2+ current in rat ventricular myocytes (a release dependent inactivation, RDI, Zahradnikova et al., 2004). We enzymatically isolated single cardiac myocytes in pulmonary vein of rabbit and applied the whole cell patch clamping technique. All procedures were accorded with national legislation. We found CDI was greatly affected by the change of Na+-Ca2+ exchange (NCX). Based on the cardiac myocyte model which could reproduce the subsarcolemmal Ca2+ dynamics (Leem et al., 2006), we reproduced CDI dynamics. We could analyze the Ca2+ binding dynamics on CaL, the subsarcolemmal Ca2+ change, and the effect of NCX and sarcoplasmic reticular (SR) Ca2+ release on CDI. The simulation results well reproduced the CDI phenomena. To reproduce CDI dynamics, it was postulated that two different Ca2+ binding sites, fast and slow, were existed and the CaL had four of each site. The simulation also reproduced the CDI dynamics in the presence and absence of NCX and the effect of SR dysfunction on CDI. In the experiment, the removal of NCX greatly increased CDI phenomena and considerably slowed the recovery from CDI. From these results, we initially thought NCX greatly modulated subsarcolemmal Ca2+ concentration and therefore, CDI was greatly affected. However, in the simulation, the NCX mainly affected the refilling extent of SR Ca2+, and affected the extent of Ca2+ release from SR which caused CDI. In conclusion, we successfully reproduced CDI phenomena in various conditions and Ca2+ release from SR is the most important factor to induce CDI. NCX could greatly modulate SR Ca2+ refilling extent and indirectly affect CDI.
Where applicable, experiments conform with Society ethical requirements