Calcium movement in cardiac mitochondria

Boyman, L., Chikando, A. C., Williams, G. S.B., Khairallah, R. J., Kettlewell, S., Ward, C. W., Smith, G. L. , Kao, J. P.Y. and Lederer, W. J. (2014) Calcium movement in cardiac mitochondria. Biophysical Journal, 107(6), pp. 1289-1301. (doi:10.1016/j.bpj.2014.07.045)

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Abstract

Existing theory suggests that mitochondria act as significant, dynamic buffers of cytosolic calcium ([Ca2+]i) in heart. These buffers can remove up to one-third of the Ca2+ that enters the cytosol during the [Ca2+]i transients that underlie contractions. However, few quantitative experiments have been presented to test this hypothesis. Here, we investigate the influence of Ca2+ movement across the inner mitochondrial membrane during both subcellular and global cellular cytosolic Ca2+ signals (i.e., Ca2+ sparks and [Ca2+]i transients, respectively) in isolated rat cardiomyocytes. By rapidly turning off the mitochondria using depolarization of the inner mitochondrial membrane potential (ΔΨm), the role of the mitochondria in buffering cytosolic Ca2+ signals was investigated. We show here that rapid loss of ΔΨm leads to no significant changes in cytosolic Ca2+ signals. Second, we make direct measurements of mitochondrial [Ca2+] ([Ca2+]m) using a mitochondrially targeted Ca2+ probe (MityCam) and these data suggest that [Ca2+]m is near the [Ca2+]i level (∼100 nM) under quiescent conditions. These two findings indicate that although the mitochondrial matrix is fully buffer-capable under quiescent conditions, it does not function as a significant dynamic buffer during physiological Ca2+ signaling. Finally, quantitative analysis using a computational model of mitochondrial Ca2+ cycling suggests that mitochondrial Ca2+ uptake would need to be at least ∼100-fold greater than the current estimates of Ca2+ influx for mitochondria to influence measurably cytosolic [Ca2+] signals under physiological conditions. Combined, these experiments and computational investigations show that mitochondrial Ca2+ uptake does not significantly alter cytosolic Ca2+ signals under normal conditions and indicates that mitochondria do not act as important dynamic buffers of [Ca2+]i under physiological conditions in heart.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Kettlewell, Dr Sarah
Authors: Boyman, L., Chikando, A. C., Williams, G. S.B., Khairallah, R. J., Kettlewell, S., Ward, C. W., Smith, G. L., Kao, J. P.Y., and Lederer, W. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Biophysical Journal
Publisher:Cell Press
ISSN:0006-3495
ISSN (Online):1542-0086

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