Faculty Collaboration Database

Extra-matrix Mg2+ limits Ca2+ uptake and modulates Ca2+ uptake-independent respiration and redox state in cardiac isolated mitochondria. J Bioenerg Biomembr 2013 Jun;45(3):203-18

Date

03/05/2013

Pubmed ID

23456198

Pubmed Central ID

PMC3670670

DOI

10.1007/s10863-013-9500-5

Scopus ID

2-s2.0-84878642065 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

Cardiac mitochondrial matrix (m) free Ca(2+) ([Ca(2+)]m) increases primarily by Ca(2+) uptake through the Ca(2+) uniporter (CU). Ca(2+) uptake via the CU is attenuated by extra-matrix (e) Mg(2+) ([Mg(2+)]e). How [Ca(2+)]m is dynamically modulated by interacting physiological levels of [Ca(2+)]e and [Mg(2+)]e and how this interaction alters bioenergetics are not well understood. We postulated that as [Mg(2+)]e modulates Ca(2+) uptake via the CU, it also alters bioenergetics in a matrix Ca(2+)-induced and matrix Ca(2+)-independent manner. To test this, we measured changes in [Ca(2+)]e, [Ca(2+)]m, [Mg(2+)]e and [Mg(2+)]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 Ca(2+) uptake and [Ca(2+)]m. Incremental [Mg(2+)]e did not reduce initial Ca(2+)uptake but attenuated the subsequent slower Ca(2+) uptake, so that [Ca(2+)]m remained unaltered over time. Adding CaCl2 without MgCl2 to attain a [Ca(2+)]m from 46 to 221 nM enhanced state 3 NADH oxidation and increased respiration by 15 %; up to 868 nM [Ca(2+)]m did not additionally enhance NADH oxidation or respiration. Adding MgCl2 did not increase [Mg(2+)]m but it altered bioenergetics by its direct effect to decrease Ca(2+) uptake. However, at a given [Ca(2+)]m, state 3 respiration was incrementally attenuated, and state 4 respiration enhanced, by higher [Mg(2+)]e. Thus, [Mg(2+)]e without a change in [Mg(2+)]m can modulate bioenergetics independently of CU-mediated Ca(2+) transport.

Author List

Boelens AD, Pradhan RK, Blomeyer CA, Camara AK, Dash RK, Stowe DF

Authors

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
David F. Stowe MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Guinea Pigs
Ion Transport
Magnesium
Membrane Potential, Mitochondrial
Mitochondria, Heart
NADP
Oxidation-Reduction
Oxygen Consumption