title: Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells.
abstract: Hypoxia contracts the pulmonary vein, but the underlying cellular effectors remain unclear. Utilizing contractile studies and whole cell patch-clamp electrophysiology, we report for the first time a hypoxia-sensitive K(+) current in porcine pulmonary vein smooth muscle cells (PVSMC). Hypoxia induced a transient contractile response that was 56 ± 7% of the control response (80 mM KCl). This contraction required extracellular Ca(2+) and was sensitive to Ca(2+) channel blockade. Blockade of K(+) channels by tetraethylammonium chloride (TEA) or 4-aminopyridine (4-AP) reversibly inhibited the hypoxia-mediated contraction. Single-isolated PVSMC (typically 159.1 ± 2.3 μm long) had mean resting membrane potentials (RMP) of -36 ± 4 mV with a mean membrane capacitance of 108 ± 3.5 pF. Whole cell patch-clamp recordings identified a rapidly activating, partially inactivating K(+) current (I(KH)) that was hypoxia, TEA, and 4-AP sensitive. I(KH) was insensitive to Penitrem A or glyburide in PVSMC and had a time to peak of 14.4 ± 3.3 ms and recovered in 67 ms following inactivation at +80 mV. Peak window current was -32 mV, suggesting that I(KH) may contribute to PVSMC RMP. The molecular identity of the potassium channel is not clear. However, RT-PCR, using porcine pulmonary artery and vein samples, identified Kv(1.5), Kv(2.1), and BK, with all three being more abundant in the PV. Both artery and vein expressed STREX, a highly conserved and hypoxia-sensitive BK channel variant. Taken together, our data support the hypothesis that hypoxic inhibition of I(KH) would contribute to hypoxic-induced contraction in PVSMC.
authors: School of Pharmacy and Life Sciences, Robert Gordon Univ, Schoolhill, Aberdeen, Scotland UK.
authors: Ciprian
authors: C
authors: Dospinescu
authors: Hélène
authors: H
authors: Widmer
authors: Iain
authors: I
authors: Rowe
authors: Cherry
authors: C
authors: Wainwright
authors: Stuart F
authors: SF
authors: Cruickshank
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D017124:Conserved Sequence; D015870:Gene Expression; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009183:Mycotoxins / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011667:Pulmonary Veins / Q000166:cytology*; D034421:Sus scrofa; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction
chemical_list: D002121:Calcium Channel Blockers; D009183:Mycotoxins; D024642:Potassium Channels, Voltage-Gated; C003626:tremortin; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D005905:Glyburide