Effects of magnesium on cardiac excitation-contraction coupling.
OBJECTIVE
Magnesium regulates a large number of cellular processes. Small changes in intracellular free Mg(2+) ([Mg(2+)](i)) may have important effects on cardiac excitability and contractility. We investigated the effects of [Mg(2+)](i) on cardiac excitation-contraction coupling.


METHODS
We used our ionic-metabolic model that incorporates equations for Ca(2+) and Mg(2+) buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps).


RESULTS
Model results indicate that variations in cytosolic Mg(2+) level might sensitively affect diastolic and systolic Ca(2+), sarcoplasmic Ca(2+) content, Ca(2+) influx through L-type channels, efficiency of the Na(+)/Ca(2+) exchanger and action potential shape. The analysis suggests that the most important reason for the observed effects is a modified normal function of sarcoplasmic Ca(2+)-ATPase pump by altered diastolic MgATP levels.


CONCLUSIONS
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.
Department of Bioengineering, PFBH 241, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA. amihaylo@bioeng.ucsd.edu
Anushka P
AP
Michailova
Mary Ellen
ME
Belik
Andrew D
AD
McCulloch
D000200:Action Potentials; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases; D004553:Electric Conductivity; D006801:Humans; D016623:Ion Pumps / Q000378:metabolism*; D017136:Ion Transport; D008274:Magnesium / Q000378:metabolism*; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D016623:Ion Pumps; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium