Negative-feedback regulation of ATP release: ATP release from cardiomyocytes is strictly regulated during ischemia

► We investigated whether ATP release was regulated during ischemia in cardiomyocytes. ► Ischemic stress rapidly increased the extracellular ATP. ► The ATP increase was reversed by treatment with blockers of maxi-anion channels. ► Maxi-anion channel blocking at later ischemia paradoxically increased ATP release. ► The increase was significantly suppressed by co-treatment with hemichannel blockers.