Sarcolemmal KATP channels in ageing

This review highlights some recent research addressing sarcolemmal KATP channels in ageing. These channels are abundant in cardiac myocytes where they are essential in coupling the cellular metabolic state with membrane excitability. The opening of sarcolemmal ATP-sensitive K+ (KATP) channels occurs during ischaemia and protect the heart against injury. Age-dependent changes in the myocardial susceptibility to ischemia have been observed in different species, including humans. Recent research has demonstrated that ageing is associated with decrease in numbers of sarcolemmal KATP in hearts from females, but not males. This phenomenon seems to be associated with age-dependent decrease in concentration of circulating estrogens. In the heart, SUR2A, a regulatory subunit of KATP channels, is present in excess over Kir6.2, a pore-forming KATP channel subunit. The consequence of this is that SUR2A is a subunit that controls the number of sarcolemmal KATP channels. Estrogens specifically up-regulate SUR2A and, thereby, control the number of sarcolemmal KATP channels. Age-dependent loss of sarcolemmal KATP channels creates a cardiac phenotype more sensitive to ischaemia, which may explain, at least in part, an ageing-associated decrease of myocardial tolerance to stress that occurs in elderly women.