10th International Magnesium Symposium Schedule of Events

25
Effects of Mg2+ on cardiac excitation-contraction coupling
Michailova AP, Belik, ME, and McCulloch, AD. Department of Bioengineering,
University of California, San Diego, USA. amihaylo@bioeng.ucsd.edu
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. For this reason, we used our ionic-metabolic model (1) - 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) – to investigate the effects of [Mg2+]i on cardiac
excitation-contraction coupling. 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. 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 (2).
1. Michailova AP, and McCulloch AD. (2001) Model Study of ATP and ADP
Buffering, Transport of Ca2+ and Mg2+, and Regulation of Ion Pumps in
Ventricular Myocyte. Biophysical Journal 81:614-629.
2. Agus ZA, Kelepouris, E, Dukes I, and Morad M. (1989) Cytosolic magnesium
modulates calcium channel activity in mammalian ventricular cells. American
Journal Physiology 256:C425-C455.