This study investigates the role of calcium-activated potassium (KCa) channels in human heart explant-derived cell (EDC) physiology and therapeutic potential. It finds that KCa3.1 channels are exclusively expressed in therapeutically bioactive EDC subfractions, maintaining a polarized resting potential. Gene transfer of *KCNN4* (encoding KCa3.1) leads to membrane hyperpolarization, increased intracellular calcium, boosted cell proliferation, and increased production of pro-healing cytokines/nanoparticles. In a murine model of ischemic cardiomyopathy, *KCNN4*-overexpressing EDCs significantly improved cardiac function, viable myocardium, and neovascularization. This suggests electrophysiological engineering as a valuable strategy to enhance cell therapy efficacy for cardioprotection.

Patrick Vigneault, Sandrine Parent, Pushpinder Kanda, Connor Michie, Darryl R. Davis, Stanley Nattel