Ion channels on the mitochondrial inner membrane influence cell function in specific ways that can be detrimental or beneficial to cell survival. At least one type of potassium (K+) channel, the mitochondrial adenosine triphosphate sensitive K+ channel (mitoK(ATP)), is an important effector of protection against necrotic and apoptotic cell injury after ischemia. Here another channel with properties similar to the surface membrane calcium-activated K+ channel was found on the mitochondrial inner membrane (mitoK(Ca)) of guinea pig ventricular cells. MitoK(Ca) significantly contributed to mitochondrial K+ uptake of the myocyte, and an opener of mitoK(Ca) protected hearts against infarction.