Effects of Mg2+, pH and PCr on cardiac excitation-metabolic coupling.

A tight coupling between ionic currents, intracellular Ca2+ homeostasis, cytosolic [ADP] and deltaG of ATP hydrolysis underlies the regulation of cardiac cell function. As more experimental detail on the biochemistry and biophysics of these complex processes and their interactions accumulates, the intuitive interpretation of the new findings becomes increasingly impractical. For this reason we developed detailed biophysical model that couples Ca2+ signaling, cell electrophysiology and bioenergetics with the main interactions between phosphorylated species (ATP, ADP, AMP, PCr, Cr, P(i)) and Lewis cytosolic acids (Na+, K+, Mg2+, H+). The results indicate that the increase in free cytosolic Mg2+ (0.2-5 mM) systematically shortens the action potential duration. The analysis suggests that that under physiological conditions a pH decrease accompanied by a free Mg2+ increase tends to counteract an [ADP] increase due to PCr depletion. The model reproduces qualitatively a sequence of events that correlates well with the experimental data.