title: Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy.
abstract: Increased pressure-induced (myogenic) tone in small uteroplacental arteries from late pregnant (LP) rats has been previously observed. In this study, we hypothesized that this response may result from a diminished activity of vascular smooth muscle cell (SMC) voltage-gated delayed-rectifier K(+) (K(v)) channels, leading to membrane depolarization, augmented Ca(2+) influx, and vasoconstriction (tone). Elevation of intraluminal pressure from 10 to 60 and 100 mmHg resulted in a marked, diltiazem-sensitive rise in SMC cytosolic Ca(2+) concentration ([Ca(2+)](i)) associated with a vasoconstriction of uteroplacental arteries of LP rats. In contrast, these changes were significantly diminished in uterine arteries from nonpregnant (NP) rats. Gestational augmentation of pressure-induced Ca(2+) influx through L-type Ca(2+) channels was associated with an enhanced SMC depolarization, the appearance of electrical and [Ca(2+)](i) oscillatory activities, and vasomotion. Exposure of vessels from NP animals to 4-aminopyridine, which inhibits the activity of K(v) channels, mimicked the effects of pregnancy by increasing pressure-induced depolarization, elevation of [Ca(2+)](i), and development of myogenic tone. Furthermore, currents through K(v) channels were significantly reduced in myocytes dissociated from arteries of LP rats compared with those of NP controls. Based on these results, we conclude that decreased K(v) channel activity contributes importantly to enhanced pressure-induced depolarization, Ca(2+) entry, and increase in myogenic tone present in uteroplacental arteries from LP rats.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The University of Vermont, Burlington, VT 05405, USA.
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Telezhkin
authors.forename: Tara
authors.initials: T
authors.lastname: Goecks
authors.forename: Adrian D
authors.initials: AD
authors.lastname: Bonev
authors.forename: George
authors.initials: G
authors.lastname: Osol
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Gokina
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D051668:Delayed Rectifier Potassium Channels; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011247:Pregnancy; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D014665:Vasodilator Agents; D015761:4-Aminopyridine; D004110:Diltiazem; D002118:Calcium