A recent study suggests that inhibition of cardiac NCX1 by protons may contribute to Ca2+ overload and reperfusion injury in the same way as the Na+-driven regulation: during experimentally-induced acidosis (pHi = 6.5), ventricular myocytes from genetically modified mice expressing a proton-insensitive mutant of NCX1 (H165A) did not show increases in Ca2+ transient amplitudes, suggesting that NCX was not inhibited and hearts from transgenic mice displayed reduced tissue damage following an ischemia–reperfusion protocol in comparison to wild-type mice [142]. The gene discussed is SLC8A1; the disease is ischemia.