Spontaneous transient outward currents and delayed rectifier K+ current: effects of hypoxia.
Single smooth muscle cells of rabbit intrapulmonary artery were voltage clamped using the perforated-patch configuration of the patch-clamp technique. We observed spontaneous transient outward currents (STOCs) and a steady-state outward current. Because STOCs were tetraethylammonium sensitive and activated by Ca2+ influx, they were believed to represent activation of Ca2+-activated K+ channels. The steady-state outward current, which was sensitive to 4-aminopyridine, was the delayed rectifier K+ current. In cells voltage clamped at 0 mV, we found that STOCs were not randomly distributed in amplitude but were composed of multiples of 1.57 +/- 0.56 pA/pF. The mean frequency of STOCs was 5.51 +/- 3.49 Hz. Ryanodine (10 microM), caffeine (5 mM), thapsigargin (200 nM), and hypoxia (PO2 = 10 mmHg) decreased STOCs. The effect of hypoxia on STOCs was partially reversible only if the experiment was conducted in the presence of thapsigargin. Hypoxia and thapsigargin decrease steady-state outward current. Thapsigargin and removal of external Ca2+ abolished the effect of hypoxia, suggesting that hypoxia decreases steady-state outward current by a Ca2+-dependent mechanism.
Unité Mixte de Recherche (UMR) Centre National de la Recherche Scientifique 6542, Physiologie des Cellules Cardiaques et Vasculaires, Faculté des Sciences, 37200 Tours Cedex, France.
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Vandier
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Delpech
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Bonnet
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012433:Ryanodine; D002110:Caffeine; D019789:Tetraethylammonium; D019284:Thapsigargin; D015761:4-Aminopyridine; D002118:Calcium