ATP- and voltage-dependent electro-metabolic signaling regulates blood flow in heart

Significance The ATP-sensitive K + channel (K ATP ) is a metabolite sensor that transduces the myocyte metabolic state into an electrical signal. Our studies show that this electro-metabolic signaling mechanism underlies the regulation of local blood flow in the heart through its actions on the contractile elements of the microvasculature. In addition, the efflux of K + supports this mechanism by its action on the capillary endothelial inward rectifier K + (Kir2.1). These findings establish a conceptually new framework for understanding the hugely reliable and incredibly robust local electro-metabolic microvascular regulation of blood flow in the heart.