title: Potassium channels regulate tone in rat pulmonary veins.
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 (K(V)) and inward rectifier (K(ir)) 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 Ba(2+), 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 K(V), K(ir), and large-conductance Ca(2+)-sensitive K(+) channels are present in PVs. Immunohistochemistry showed that K(ir) 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 K(ir) channels, which may modulate venous return both physiologically and in disease states including pulmonary edema.
authors.affiliation: Department of Medicine (Cardiology), University of Alberta, Edmonton, Alberta T6G 2B7, Canada. emichela@cha.ab.ca
authors.forename: E D
authors.initials: ED
authors.lastname: Michelakis
authors.forename: E K
authors.initials: EK
authors.lastname: Weir
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Nsair
authors.forename: R
authors.initials: R
authors.lastname: Waite
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: L
authors.initials: L
authors.lastname: Puttagunta
authors.forename: H G
authors.initials: HG
authors.lastname: Knaus
authors.forename: S L
authors.initials: SL
authors.lastname: Archer
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002469:Cell Separation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011652:Pulmonary Circulation / Q000502:physiology; D011667:Pulmonary Veins / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: C510692:Kcnj1 protein, rat; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D001464:Barium; D019789:Tetraethylammonium; C064719:iberiotoxin; D015761:4-Aminopyridine; D005905:Glyburide