Susceptibility of ATP-sensitive K+ channels to cell stress through mediation of phosphoinositides as examined by photoirradiation.
Cell stress is implicated in a number of pathological states of metabolism, such as ischaemia, reperfusion and apoptosis in heart, neurons and other tissues. While it is known that the ATP-sensitive K+ (KATP) channel plays 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 cloned KATP channels. Single KATP channel currents were recorded from cell-attached and inside-out patches of rat ventricular myocytes and COS-1 cells coexpressing SUR2 and Kir6.2. KATP channel activity increased within < 1 min upon irradiation. The activity resulted from increased maximal open probability and decreased ATP inhibition. The effects remained after the irradiation was stopped. Irradiation also affected the channels formed only by Kir6.2DeltaC35. The irradiation-induced activation was comparable to that induced by phosphoinositides. Analysis of phosphatidylinositol composition revealed an elevated phosphatidylinositol bisphosphate level with irradiation. Wortmannin, an inhibitor of phosphatidylinositol kinases, decreased both the irradiation-induced channel activity and the production of phosphatidylinositol bisphosphates. Radical scavengers also reduced the irradiation-induced activation, suggesting a role for free radicals, an immediate product of photoirradiation. We conclude that photoirradiation can modify the single-channel properties of KATP, which appears to be mediated by phosphoinositides. Our study suggests that cellular stress may be linked with KATP channels, and we offer a putative mechanism for such a linkage.
Fan
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The Department of Physiology, University of Tennessee, College of Medicine, Memphis, TN 38163, USA. zfan@physio1.utmem.edu
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D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D002417:Cattle; D004553:Electric Conductivity; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008027:Light; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010716:Phosphatidylinositols / Q000494:pharmacology / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; C577512:Abcc9 protein, rat; D016166:Free Radical Scavengers; D010716:Phosphatidylinositols; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate