Susceptibility of ATP-sensitive K+ channels to cell stress through mediation of phosphoinositides as examined by photoirradiation

1. Cell stress is implicated in a number of pathological states of metaboli sm, such as ischaemia, reperfusion and apoptosis in heart, neurons and othe r tissues. While it is known that the ATP-sensitive K+ (K-ATP) channel play s a role during metabolic abnormality little information is available about the direct response of this channel to cell stress. Using photoirradiation stimulation, we studied the effects of cell stress on both native and clon ed K-ATP channels. 2. Single K-ATP channel currents were recorded from cell-attached and insid e-out patches of rat ventricular myocytes and COS-1 cells coexpressing SUR2 and Kir6.2. K-ATP channel activity increased within < 1 min upon irradiati on. The activity resulted from increased maximal open probability and decre ased ATP inhibition. The effects remained after the irradiation was stopped . Irradiation also affected the channels formed only by Kir6.2<Delta>C35. 3. The irradiation-induced activation was comparable to that induced by pho sphoinositides. Analysis of phosphatidylinositol composition revealed an el evated phosphatidylinositol bisphosphate level with irradiation. Wortmannin , an inhibitor of phosphatidglinosital kinsases, decreased both the irradia tion-induced channel activity and the production of phosphatidylinositol bi sphosphates. 4. Radical scavengers also reduced the irradiation-induced activation, sugg esting a role for free radicals, an immediate product of photoirradiation. 5. We conclude that photoirradiation can modify the single-channel properti es of K-ATP, which appears to be mediated by phosphoinositides. Our study s uggests that cellular stress may be linked with K-ATP channels, and we offe r a putative mechanism for such a linkage.