Ageing, gender and cardiac sarcolemmal K(ATP) channels.
Sarcolemmal ATP-sensitive K(+) (K(ATP)) channels are abundant in cardiac myocytes where they couple the cellular metabolic state with membrane excitability. Structurally, these channels are composed of Kir6.2, a pore-forming subunit, SUR2A, a regulatory subunit, and at least four accessory proteins. The activation of K(ATP) channels occurs during ischaemia to promote cardiac viability under this adverse condition. Age-dependent changes in the myocardial susceptibility to ischaemia have been reported in experimental animals as well as in humans. Recent research has demonstrated that ageing is associated with a decrease in the number of cardiac sarcolemmal K(ATP) channels in hearts from females, but not males. This alteration is likely to be due to an age-dependent decrease in the concentration of circulating estrogens. In the heart, SUR2A is the least expressed protein of all K(ATP) channel-forming proteins. The consequence of this phenomenon is that the level of SUR2A is the main factor controlling the number of sarcolemmal K(ATP) channels. Estrogens specifically up-regulate SUR2A and govern the number of sarcolemmal K(ATP) channels, and this may explain the effect of decreasing estrogen levels on the heart. An age-dependent decrease in the number of sarcolemmal K(ATP) channels generates a cardiac phenotype more sensitive to ischaemia, which seems to be responsible for the ageing-associated decrease in myocardial tolerance to stress that occurs in elderly women.
Jovanović
Aleksandar
A
Maternal and Child Health Sciences, Tayside Institute of Child Health, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. a.jovanovic@dundee.ac.uk
D000375:Aging / Q000502:physiology*; D000818:Animals; D005260:Female; D006321:Heart / Q000503:physiopathology; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism / Q000502:physiology*; D012508:Sarcolemma / Q000378:metabolism*; D012737:Sex Factors
D024661:Potassium Channels, Inwardly Rectifying