| 17982020 |
Telezhkin V, Goecks T, Bonev AD, Osol G, Gokina NI: Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy. Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H272-84. Epub 2007 Nov 2.
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. |
1(0,0,0,1) |