Mg²⁺ Differentially Regulates Two Modes of Mitochondrial Ca²⁺ Uptake in Isolated Cardiac Mitochondria: Implications for Mitochondrial Ca²⁺ Sequestration

Authors

Christoph A. Blomeyer, Medical College of Wisconsin
Jason Bazil, University of Michigan - Ann Arbor
David F. Stowe, Marquette University
Ranjan K. Dash, Medical College of Wisconsin
Amadou KS Camara, Medical College of Wisconsin

Document Type

Article

Language

eng

Format of Original

14 p.

Publication Date

6-2016

Publisher

Springer Verlag

Source Publication

Journal of Bioenergetics and Biomembranes

Source ISSN

0145-479x

Original Item ID

DOI: 10.1007/s10863-016-9644-1

Abstract

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.

Comments

Accepted version. Journal of Bioenergetics and Biomembranes, Vol. 48, No. 3 (June 2016): 175-188. DOI. © 2016 Springer Science+Business Media. Used with permission.

The final publication is available at Springer via http://dx.doi.org/10.1007/s10863-016-9644-1.

David F. Stowe was also affiliated with the Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center at the time of publication.

Ranjan K. Dash was also affiliated with the Medical College of Wisconsin at the time of publication.

Shareable Link. Provided by the Springer Nature SharedIt content-sharing initiative.

Recommended Citation

Blomeyer, Christoph A.; Bazil, Jason; Stowe, David F.; Dash, Ranjan K.; and Camara, Amadou KS, "Mg²⁺ Differentially Regulates Two Modes of Mitochondrial Ca²⁺ Uptake in Isolated Cardiac Mitochondria: Implications for Mitochondrial Ca²⁺ Sequestration" (2016). Biomedical Engineering Faculty Research and Publications. 405.
https://epublications.marquette.edu/bioengin_fac/405