NCX inhibitors (Na+ / Ca2+ exchange inhibitors) to limit ischemic injury

NCX inhibitors (Na+ / Ca2+ exchange inhibitors) to limit ischemic injury

Elevation of calcium levels in the cells is an important mechanism of ischemic cellular injury and death. Na⁺ / Ca²⁺ exchanger (NCX) has the main role in elevating calcium levels within the myocardial cells during ischemia and reperfusion. Hence NCX inhibitors have been considered to be potential novel agents for limiting hypoxic cell injury.

Three genes encoding for NCX in the human genome are NCX1, NCX2 and NCX3. NCX1 is present in heart, brain and kidney. NCX2 and NCX3 are seen in brain and skeletal muscle. It is interesting to note that while NCX1 knockout is embryonically lethal, NCX2 knockout increases hippocampal long term potentiation and improves performance on learning and memory tests.
Though homozygous NCX1 knockouts are embryonic lethal, heterozygote NCX1 knockouts are viable. These transgenic mice have reduced NCX protein levels and have lesser rise of calcium levels within the cells after hypoxia and have a reduced susceptibility to ischemic injury.