Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells

Dospinescu, C., Widmer, H., Rowe, I. , Wainwright, C. and Cruickshank, S. F. (2012) Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells. American Journal of Physiology: Lung Cellular and Molecular Physiology, 303(5), L476-L486. (doi: 10.1152/ajplung.00157.2012) (PMID:22773694)

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 Ca2+ and was sensitive to Ca2+ 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 (IKH) that was hypoxia, TEA, and 4-AP sensitive. IKH 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 IKH 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 Kv1.5, Kv2.1, 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 IKH would contribute to hypoxic-induced contraction in PVSMC.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rowe, Dr Iain
• Authors: Dospinescu, C., Widmer, H., Rowe, I., Wainwright, C., and Cruickshank, S. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: American Journal of Physiology: Lung Cellular and Molecular Physiology
• Publisher: American Physiological Society
• ISSN: 1040-0605
• ISSN (Online): 1522-1504