Cardiac myocytes were differentiated in vitro from cultured embryonic stem cells derived from mice. The cultured cells displayed spontaneous beating. Like adult pacemaker cells, the embryonic stem cell derived cells were found to display wave-like spontaneous calcium oscillations which entrain with whole-cell action potentials by means of sodium-calcium exchange. As in sino-atrial node cells, these oscillations were promoted by elevation of intracellular cyclic AMP. This suggests that cells engineered to have constitutively high cAMP levels could form robust pacemakers.
