A Computational Model of Cytosolic and Mitochondrial Ca2+ in Paced Rat Ventricular Myocytes.
10.4196/kjpp.2011.15.4.217
- Author:
Jae Boum YOUM
1
;
Seong Woo CHOI
;
Chang Han JANG
;
Hyoung Kyu KIM
;
Chae Hun LEEM
;
Nari KIM
;
Jin HAN
Author Information
1. National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea. youmjb@inje.ac.kr
- Publication Type:Original Article
- Keywords:
Mitochondria;
Ca2+ transient;
Rat ventricular myocytes;
Computational model
- MeSH:
Animals;
Computer Simulation;
Cytosol;
Hydrazones;
Ion Transport;
Membranes;
Mitochondria;
Mitochondrial Membranes;
Muscle Cells;
Nitriles;
Rats
- From:The Korean Journal of Physiology and Pharmacology
2011;15(4):217-239
- CountryRepublic of Korea
- Language:English
-
Abstract:
We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial Ca2+ transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1~3 Hz) made both the diastolic and systolic [Ca2+] bigger in mitochondria as well as in cytosol. As L-type Ca2+ channel has key influence on the amplitude of Ca2+-induced Ca2+ release, the relation between stimulus frequency and the amplitude of Ca2+ transients was examined under the low density (1/10 of control) of L-type Ca2+ channel in model simulation, where the relation was reversed. In experiment, block of Ca2+ uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial Ca2+ transients, while it failed to affect the cytosolic Ca2+ transients. In computer simulation, the amplitude of cytosolic Ca2+ transients was not affected by removal of Ca2+ uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [Ca2+] in cytosol and eventually abolished the Ca2+ transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type Ca2+ channel to total transsarcolemmal Ca2+ flux could determine whether the cytosolic Ca2+ transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic Ca2+ affects mitochondrial Ca2+ in a beat-to-beat manner, however, removal of Ca2+ influx mechanism into mitochondria does not affect the amplitude of cytosolic Ca2+ transients.
