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Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2012 Sep; Vol. 303 (5), pp. L476-86. Date of Electronic Publication: 2012 Jul 06. - Publication Year :
- 2012
-
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.
- Subjects :
- 4-Aminopyridine pharmacology
Amino Acid Sequence
Animals
Calcium Channel Blockers pharmacology
Cell Hypoxia
Cells, Cultured
Conserved Sequence
Gene Expression
Glyburide pharmacology
In Vitro Techniques
Molecular Sequence Data
Mycotoxins pharmacology
Myocytes, Smooth Muscle drug effects
Myocytes, Smooth Muscle metabolism
Patch-Clamp Techniques
Potassium Channels, Voltage-Gated antagonists & inhibitors
Potassium Channels, Voltage-Gated genetics
Sus scrofa
Tetraethylammonium pharmacology
Vasoconstriction
Membrane Potentials
Myocytes, Smooth Muscle physiology
Potassium Channels, Voltage-Gated metabolism
Pulmonary Veins cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1504
- Volume :
- 303
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 22773694
- Full Text :
- https://doi.org/10.1152/ajplung.00157.2012