Journal of Bioenergetics and Biomembranes

, Volume 48, Issue 3, pp 175–188 | Cite as

Mg2+ differentially regulates two modes of mitochondrial Ca2+ uptake in isolated cardiac mitochondria: implications for mitochondrial Ca2+ sequestration

  • Christoph A. Blomeyer
  • Jason N. Bazil
  • David F. Stowe
  • Ranjan K. Dash
  • Amadou K. S. Camara


The manner in which mitochondria take up and store Ca2+ remains highly debated. Recent experimental and computational evidence has suggested the presence of at least two modes of Ca2+ uptake and a complex Ca2+ sequestration mechanism in mitochondria. But how Mg2+ regulates these different modes of Ca2+ uptake as well as mitochondrial Ca2+ sequestration is not known. In this study, we investigated two different ways by which mitochondria take up and sequester Ca2+ by using two different protocols. Isolated guinea pig cardiac mitochondria were exposed to varying concentrations of CaCl2 in the presence or absence of MgCl2. In the first protocol, A, CaCl2 was added to the respiration buffer containing isolated mitochondria, whereas in the second protocol, B, mitochondria were added to the respiration buffer with CaCl2 already present. Protocol A resulted first in a fast transitory uptake followed by a slow gradual uptake. In contrast, protocol B only revealed a slow and gradual Ca2+ uptake, which was approximately 40 % of the slow uptake rate observed in protocol A. These two types of Ca2+ uptake modes were differentially modulated by extra-matrix Mg2+. That is, Mg2+ markedly inhibited the slow mode of Ca2+ uptake in both protocols in a concentration-dependent manner, but not the fast mode of uptake exhibited in protocol A. Mg2+ also inhibited Na+-dependent Ca2+ extrusion. The general Ca2+ binding properties of the mitochondrial Ca2+ sequestration system were reaffirmed and shown to be independent of the mode of Ca2+ uptake, i.e. through the fast or slow mode of uptake. In addition, extra-matrix Mg2+ hindered Ca2+ sequestration. Our results indicate that mitochondria exhibit different modes of Ca2+ uptake depending on the nature of exposure to extra-matrix Ca2+, which are differentially sensitive to Mg2+. The implications of these findings in cardiomyocytes are discussed.


Mitochondria Cardiac Calcium uptake Calcium sequestration Calcium efflux 



This work was funded by NIH grants R01-HL095122, P01-GM066730, and K99-HL121160.

Supplementary material

10863_2016_9644_MOESM1_ESM.docx (1.6 mb)
ESM 1 (DOCX 1622 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Christoph A. Blomeyer
    • 1
  • Jason N. Bazil
    • 2
    • 3
    • 4
  • David F. Stowe
    • 1
    • 4
    • 5
    • 6
  • Ranjan K. Dash
    • 3
    • 4
    • 5
  • Amadou K. S. Camara
    • 1
  1. 1.Department of AnesthesiologyMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of Molecular and Integrative PhysiologyUniversity of MichiganAnn ArborUSA
  3. 3.Biotechnology and Bioengineering CenterMedical College of WisconsinMilwaukeeUSA
  4. 4.Department of PhysiologyMedical College of WisconsinMilwaukeeUSA
  5. 5.Department of Biomedical EngineeringMarquette UniversityMilwaukeeUSA
  6. 6.Research ServiceZablocki Veterans Affairs Medical CenterMilwaukeeUSA

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