Role of ATP sensitive potassium channels in long term adaptation to metabolic stress.

Cardiac KATP channel activation during metabolic inhibition has been implicated in effects ranging from malignant arrhythmogenesis and sudden cardiac death to reduction in infarct size, preconditioning, and a more rapid recovery of contractile ability. Given these disparate consequences, and the repeated observation that KATP currents are altered under a wide variety of metabolically stressful conditions, it becomes increasingly more critical to determine whether the changes described are part of the underlying pathology, or whether they reflect an endogenous adaptation to protect cardiac function. We support the view that enhanced KATP channels are intrinsically altered during long term metabolic inhibition, at least in part through a reduction in channel sensitivity to ATP, and that the change manifests itself in most cases as an adaptive mechanism. Increased channel activity in a chronically ischaemic environment could serve to maintain resting potential, limit calcium influx, conserve [ATP]i, and prevent excessive prolongation of action potential duration.