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Effects of Magnesium on Cardiac Excitation-Contraction Coupling

Department of Bioengineering, University of California San Diego, La Jolla CA, USA

Address reprint requests to: Anushka Michailova, Ph.D., Department of Bioengineering, PFBH 241, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412. E-mail: amihaylo{at}bioeng.ucsd.edu

Objective: Magnesium regulates a large number of cellular processes. Small changes in intracellular free Mg²⁺ ([Mg²⁺]_i) may have important effects on cardiac excitability and contractility. We investigated the effects of [Mg²⁺]_i on cardiac excitation-contraction coupling.

Methods: We used our ionic-metabolic model that incorporates equations for Ca²⁺ and Mg²⁺ buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na⁺-K⁺ pump, sarcolemmal and sarcoplasmic Ca²⁺ pumps).

Results: Model results indicate that variations in cytosolic Mg²⁺ level might sensitively affect diastolic and systolic Ca²⁺, sarcoplasmic Ca²⁺ content, Ca²⁺ influx through L-type channels, efficiency of the Na⁺/Ca²⁺ exchanger and action potential shape. The analysis suggests that the most important reason for the observed effects is a modified normal function of sarcoplasmic Ca²⁺-ATPase pump by altered diastolic MgATP levels.

Conclusion: The model is able to reproduce qualitatively a sequence of events that correspond well with experimental observations during cardiac excitation-contraction coupling in mammalian ventricular myocytes.

Key words: Mg²⁺, Ca²⁺, cardiac excitation-contraction coupling, computer modelling

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