Boelens 2013 J Bioenerg Biomembr

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Boelens AD, Pradhan RK, Blomeyer CA, Camara AK, Dash RK, Stowe DF (2013) Extra-matrix Mg2+ limits Ca2+ uptake and modulates Ca2+ uptake-independent respiration and redox state in cardiac isolated mitochondria. J Bioenerg Biomembr 45:203-18.

» PMID: 23456198 Open Access

Boelens AD, Pradhan RK, Blomeyer CA, Camara AK, Dash RK, Stowe DF (2013) J Bioenerg Biomembr

Abstract: Cardiac mitochondrial matrix (m) free Ca2+ ([Ca2+]m) increases primarily by Ca2+ uptake through the Ca2+ uniporter (CU). Ca2+ uptake via the CU is attenuated by extra-matrix (e) Mg2+ ([Mg2+]e). How [Ca2+]m is dynamically modulated by interacting physiological levels of [Ca2+]e and [Mg2+]e and how this interaction alters bioenergetics are not well understood. We postulated that as [Mg2+]e modulates Ca2+ uptake via the CU, it also alters bioenergetics in a matrix Ca2+-induced and matrix Ca2+-independent manner. To test this, we measured changes in [Ca2+]e, [Ca2+]m, [Mg2+]e and [Mg2+]m spectrofluorometrically in guinea pig cardiac mitochondria in response to added CaCl2 (0-0.6 mM; 1 mM EGTA buffer) with/without added MgCl2 (0-2 mM). In parallel, we assessed effects of added CaCl2 and MgCl2 on NADH, membrane potential (ΔΨm), and respiration. We found that ≥0.125 mM MgCl2 significantly attenuated CU-mediated Ca2+ uptake and [Ca2+]m. Incremental [Mg2+]e did not reduce initial Ca2+ uptake but attenuated the subsequent slower Ca2+ uptake, so that [Ca2+]m remained unaltered over time. Adding CaCl2 without MgCl2 to attain a [Ca2+]m from 46 to 221 nM enhanced state 3 NADH oxidation and increased respiration by 15 %; up to 868 nM [Ca2+]m did not additionally enhance NADH oxidation or respiration. Adding MgCl2 did not increase [Mg2+]m but it altered bioenergetics by its direct effect to decrease Ca2+ uptake. However, at a given [Ca2+]m, state 3 respiration was incrementally attenuated, and state 4 respiration enhanced, by higher [Mg2+]e. Thus, [Mg2+]e without a change in [Mg2+]m can modulate bioenergetics independently of CU-mediated Ca2+ transport.

Keywords: Cardiac mitochondria, Inner mitochondrial membrane, Bioenergetics, Ca2+ uniporter, Ca2+ uptake, Mg2+ inhibition

O2k-Network Lab: US WI Milwaukee Dash RK


Labels: MiParea: Respiration 


Organism: Guinea pig  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Regulation: Calcium, Redox state  Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k