[citation needed] One significant implication of the link between cellular oxidative stress and increased KATP production is that overall potassium transport function is directly proportional to the membrane concentration of these channels.
In cases of diabetes, KATP channels cannot function properly, and a marked sensitivity to mild cardiac ischemia and hypoxia results from the cells' inability to adapt to adverse oxidative conditions.
This helps restore proper membrane potential, allowing further H+ outflow, which continues to provide the proton gradient necessary for mitochondrial ATP synthesis.
Without aid from the potassium channels, the depletion of high energy phosphate would outpace the rate at which ATP could be created against an unfavorable electrochemical gradient.
In order to conserve energy, sarcKATP open, reducing the duration of the action potential while nucKATP-mediated Ca2+ concentration changes within the nucleus favor the expression of protective protein genes.
[8] Cardiac ischemia, while not always immediately lethal, often leads to delayed cardiomyocyte death by necrosis, causing permanent injury to the heart muscle.
One method, first described by Keith Reimer in 1986, involves subjecting the affected tissue to brief, non-lethal periods of ischemia (3–5 minutes) before the major ischemic insult.
This baseline protection is believed to be a result of sarcKATP's ability to prevent cellular Ca2+ overloading and depression of force development during muscle contraction, thereby conserving scarce energy resources.
[26] Absence of sarcKATP, in addition to attenuating the benefits of IPC, significantly impairs the myocyte's ability to properly distribute Ca2+, decreasing sensitivity to sympathetic nerve signals, and predisposing the subject to arrhythmia and sudden death.
[27] Similarly, sarcKATP regulates vascular smooth muscle tone, and deletion of the kir6.2 or sur2 genes leads to coronary artery vasospasm and death.
[28] Upon further exploration of sarcKATP's role in cardiac rhythm regulation, it was discovered that mutant forms of the channel, particularly mutations in the SUR2 subunit, were responsible for dilated cardiomyopathy, especially after ischemia/reperfusion.
Increased potassium conductance should stabilize membrane potential during ischemic insults, reducing the extent infarct and ectopic pacemaker activity.