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KMID : 0811720110150040217
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Korean Journal of Physiology & Pharmacology
2011 Volume.15 No. 4 p.217 ~ p.239
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A Computational Model of Cytosolic and Mitochondrial [Ca2＋] in Paced Rat Ventricular Myocytes
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Youm Jae-Boum
Choi Seong-Woo
Jang Chang-Han
Kim Hyoung-Kyu
Kim Na-Ri
Han Jin
Leem Chae-Hun
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Abstract
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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.
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KEYWORD
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Mitochondria, Ca2＋ transient, Rat ventricular myocytes, Computational model
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