Activation of ATP-dependent K+ channels by hypoxia in smooth muscle cells isolated from the pig coronary artery.
1. The perforated patch technique with amphotericin B was used to record whole-cell currents activated by hypoxia in smooth muscle cells, isolated enzymatically from pig coronary arteries. 2. Superfusion with hypoxic solution (O2 partial pressure, 25-40 mmHg) activated an inward current at -60 mV in 143 mM extracellular K+. The reversal potential of the current induced by hypoxia shifted with extracellular [K+] as expected for a K+ current, while its current-voltage relation was consistent with the channels showing little voltage dependence. 3. The hypoxia-induced current was inhibited by glibenclamide (10 microM), but was unaffected by charybdotoxin (50 nM). 4. In whole-cell recordings at -60 mV in 143 mM K+ solution, openings of single channels passing a current close to -2 pA could sometimes be detected in normoxic solution. Openings became more frequent during the onset of the response to hypoxia, when several levels could be detected. Channels with a similar conductance were activated by hypoxia in cell-attached patches. 5. Our results suggest that hypoxia activates ATP-dependent K+ channels. We discuss possible mechanisms by which this activation may occur.
Dart
C
C
Department of Cell Physiology and Pharmacology, University of Leicester, UK.
Standen
N B
NB
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002469:Cell Separation; D018999:Charybdotoxin; D003331:Coronary Vessels; D005905:Glyburide / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D012604:Scorpion Venoms / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000502:physiology
D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D000666:Amphotericin B; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide