Characterization of Different Modes of Ca2+ Uptake under Different Physiological Conditions in the Heart Mitochondria

2013-06-18T21:42:02Z (GMT) by Shiv Tewari
<p>Cardiac mitochondria can act as a significant Ca2+ sink and shape the cytosolic Ca2+ signals affecting various cellular processes such as energy metabolism and excitation-contraction coupling. However, mitochondrial Ca2+ uptake mechanisms under different (patho)physio-logical conditions are not well understood. Characterization of these mechanisms is crucial in developing a quantitative understanding of Ca2+ signals in the heart. For this purpose, we performed Ca2+ uptake experiments in isolated guinea pig heart mitochondria under different experimental concentrations of extra-matrix Mg2+ and Ca2+. The Na+ free respiration buffer contained 1 mM EGTA with variable levels of Mg2+ (0 mM–2 mM) and CaCl2 (0.0 mM–0.6 mM) was added as a pulse after mitochondrial energization with substrate was pyruvic acid. Experimental data were analyzed using an integrated model of mitochondrial bioenergetics and cation handling. Our model analyses of the data reveal the existence of two Ca2+ uniporters or Ca2+ uptake pathways, namely a fast CU (fCU) and a slow CU (sCU), which exhibit contrasting differences in [Ca2+]e and [Mg2+]e sensitivities. fCU is a time-dependent high affinity Ca2+ uniporter, while sCU is a time-independent low affinity Ca2+ uniporter. Both uniporters are inhibited by extra-matrix Mg2+. The binding affinity of fCU for Mg2+ is higher as compared to that of sCU.</p>



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