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Hypoxia Sensitivity of a Voltage-Gated Potassium Current in Porcine Intrapulmonary Vein Smooth Muscle Cells

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Dospinescu C, Widmer H, Rowe I, Wainwright C, Cruickshank SF

Editorial: Am J Physiol Lung Cell Mol Physiol, 2012.

Rezumat:

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 41±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 TEA or 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±3.5pF. 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 -32mV, suggesting I(KH) may contribute to PVSMC resting membrane potential. The molecular identity of the potassium current 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 pulmonary vein. 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 IKH would contribute to hypoxic induced contraction in PVSMC.

Cuvinte cheie: hypoxia, pulmonary vein, smooth muscle cells

URL: http://www.ncbi.nlm.nih.gov/pubmed/22773694