Experimental and Theoretical Work on Excitation and Excitation-contraction Coupling in the Heart

A combination of experimental and theoretical work has been used to investigate the movements of calcium during cardiac excitation. In addition to calcium entry through several types of calcium channel, calcium efflux occurs to balance the entry during each cycle of activity. Measurements of net membrane calcium movements have been made with the right time resolution by Don Hilgemann in Los Angeles by investigating fast extracellular calcium transients. This work shows that, in mammalian cardiac cells, net calcium exit occurs quite early during repolarization and is nearly complete by the time the resting potential is re-established. These results correlate very well indeed with measurements made in the Oxford laboratory of calcium-activated inward current in single cardiac myocytes. Both approaches are consistent with the view that calcium efflux occurs largely through the sodium-calcium exchange process. Modelling of this process in equations developed recently with Dario DiFrancesco, Susan Noble and Don Hilgemann succeeds in reproducing both the ionic current changes and the fast extracellular calcium transients.