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Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy

Departments of Obstetrics and Gynecology, and Pharmacology, University of Vermont, College of Medicine, Burlington, Vermont

Submitted 19 February 2007 ; accepted in final form 28 October 2007

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 Ca²⁺ 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 Ca²⁺ concentration ([Ca²⁺]_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 Ca²⁺ influx through L-type Ca²⁺ channels was associated with an enhanced SMC depolarization, the appearance of electrical and [Ca²⁺]_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 [Ca²⁺]_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, Ca²⁺ entry, and increase in myogenic tone present in uteroplacental arteries from LP rats.

membrane potential; intracellular calcium; patch clamp; potassium currents; 4-aminopyridine

This article has been cited by other articles:

				N. I. Gokina, O. Y. Kuzina, R. Fuller, and G. Osol Local Uteroplacental Influences are Responsible for the Induction of Uterine Artery Myogenic Tone during Rat Pregnancy Reproductive Sciences, November 1, 2009; 16(11): 1072 - 1081. [Abstract] [PDF]