Potassium channels regulate tone in rat pulmonary veins

Author:

Michelakis Evangelos D.1,Weir E. Kenneth2,Wu Xichen1,Nsair Ali1,Waite Ross1,Hashimoto Kyoko1,Puttagunta Lakshmi3,Knaus Hans Gunther4,Archer Stephen L.1

Affiliation:

1. Departments of Medicine (Cardiology) and

2. Department of Medicine (Cardiology), Veterans Affairs Medical Center, Minneapolis, Minnesota 55455; and

3. Pathology, University of Alberta, Edmonton, Alberta T6G 2B7, Canada;

4. Department of Biochemical Pharmacology, University of Innsbruck, Innsbruck 6020, Austria

Abstract

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.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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