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Am J Physiol Lung Cell Mol Physiol 280: L1138-L1147, 2001;
1040-0605/01 $5.00
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Vol. 280, Issue 6, L1138-L1147, June 2001

Potassium channels regulate tone in rat pulmonary veins

Evangelos D. Michelakis1, E. Kenneth Weir2, Xichen Wu1, Ali Nsair1, Ross Waite1, Kyoko Hashimoto1, Lakshmi Puttagunta3, Hans Gunther Knaus4, and Stephen L. Archer1

Departments of 1 Medicine (Cardiology) and 3 Pathology, University of Alberta, Edmonton, Alberta T6G 2B7, Canada; 2 Department of Medicine (Cardiology), Veterans Affairs Medical Center, Minneapolis, Minnesota 55455; and 4 Department of Biochemical Pharmacology, University of Innsbruck, Innsbruck 6020, Austria

Intrapulmonary veins (PVs) contribute to pulmonary vascular resistance, but the mechanisms controlling PV tone are poorly understood. Although smooth muscle cell (SMC) K+ channels regulate tone in most vascular beds, their role in PV tone is unknown. We show that voltage-gated (KV) and inward rectifier (Kir) K+ channels control resting PV tone in the rat. PVs have a coaxial structure, with layers of cardiomyocytes (CMs) arrayed externally around a subendothelial layer of typical SMCs, thus forming spinchterlike structures. PVCMs have both an inward current, inhibited by low-dose Ba2+, and an outward current, inhibited by 4-aminopyridine. In contrast, PVSMCs lack inward currents, and their outward current is inhibited by tetraethylammonium (5 mM) and 4-aminopyridine. Several KV, Kir, and large-conductance Ca2+-sensitive K+ channels are present in PVs. Immunohistochemistry showed that Kir channels are present in PVCMs and PV endothelial cells but not in PVSMCs. We conclude that K+ channels are present and functionally important in rat PVs. PVCMs form sphincters rich in Kir channels, which may modulate venous return both physiologically and in disease states including pulmonary edema.

inward rectifier potassium channels; voltage-gated potassium channels; venous tone; pulmonary circulation; pulmonary edema


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