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Characterization of Different Modes of Ca 2+ Uptake under Physiological Conditions in Heart Mitochondria
Author(s) -
Tewari Shivendra,
Pradhan Ranjan K,
Bazil Jason N,
Camara Amadou KS,
Stowe David F,
Beard Daniel A,
Dash Ranjan K
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1209.20
Subject(s) - uniporter , mitochondrion , biophysics , egta , chemistry , cytosol , mitochondrial matrix , bioenergetics , calcium , biochemistry , biology , enzyme , organic chemistry
Cardiac mitochondria can act as a significant Ca 2+ sink and shape cytosolic Ca 2+ signals that affect various cellular processes such as energy metabolism and excitation‐contraction coupling. However, mitochondrial Ca 2+ uptake mechanisms under physiological conditions are not well understood. Characterization of these mechanisms is crucial in developing a quantitative understanding of Ca 2+ transients in the heart. For this purpose, we performed Ca 2+ uptake experiments in isolated guinea pig heart mitochondria at physiological concentrations of extra‐matrix Mg 2+ (0–2 mM MgCl 2 ) and Ca 2+ (0–0.6 mM CaCl 2 ) with 1 mM EGTA. Experimental data were quantified using an integrated model of mitochondrial bioenergetics and cation handling, including our recently developed models of mitochondrial Ca 2+ uniporter and Ca 2+ sequestration system. Our model analyses reveal the existence of two Ca 2+ uniporters, a fast CU (fCU) and a slow CU (sCU), with contrasting differences in their Ca 2+ and Mg 2+ sensitivities. fCU is a high affinity low capacity Ca 2+ uniporter, while sCU is a low affinity high capacity Ca 2+ uniporter. Both uniporters are inhibited by extra‐matrix Mg 2+ . The Mg 2+ binding affinity of fCU is higher as compared to that of sCU.