TITLE

Extra-matrix Mg limits Ca uptake and modulates Ca uptake-independent respiration and redox state in cardiac isolated mitochondria

AUTHOR(S)
Boelens, Age; Pradhan, Ranjan; Blomeyer, Christoph; Camara, Amadou; Dash, Ranjan; Stowe, David
PUB. DATE
June 2013
SOURCE
Journal of Bioenergetics & Biomembranes;Jun2013, Vol. 45 Issue 3, p203
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Cardiac mitochondrial matrix (m) free Ca ([Ca]) increases primarily by Ca uptake through the Ca uniporter (CU). Ca uptake via the CU is attenuated by extra-matrix (e) Mg ([Mg]). How [Ca] is dynamically modulated by interacting physiological levels of [Ca] and [Mg] and how this interaction alters bioenergetics are not well understood. We postulated that as [Mg] modulates Ca uptake via the CU, it also alters bioenergetics in a matrix Ca-induced and matrix Ca-independent manner. To test this, we measured changes in [Ca], [Ca], [Mg] and [Mg] spectrofluorometrically in guinea pig cardiac mitochondria in response to added CaCl (0-0.6 mM; 1 mM EGTA buffer) with/without added MgCl (0-2 mM). In parallel, we assessed effects of added CaCl and MgCl on NADH, membrane potential (ΔΨ), and respiration. We found that >0.125 mM MgCl significantly attenuated CU-mediated Ca uptake and [Ca]. Incremental [Mg] did not reduce initial Cauptake but attenuated the subsequent slower Ca uptake, so that [Ca] remained unaltered over time. Adding CaCl without MgCl to attain a [Ca] from 46 to 221 nM enhanced state 3 NADH oxidation and increased respiration by 15 %; up to 868 nM [Ca] did not additionally enhance NADH oxidation or respiration. Adding MgCl did not increase [Mg] but it altered bioenergetics by its direct effect to decrease Ca uptake. However, at a given [Ca], state 3 respiration was incrementally attenuated, and state 4 respiration enhanced, by higher [Mg]. Thus, [Mg] without a change in [Mg] can modulate bioenergetics independently of CU-mediated Ca transport.
ACCESSION #
87845991

 

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