The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of...

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Published in:	Reproductive biology and endocrinology Vol. 5; no. 1; p. 41
Main Authors:	Smith, Ryan C, McClure, Marisa C, Smith, Margaret A, Abel, Peter W, Bradley, Michael E
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 02-11-2007 BioMed Central BMC
Subjects:	4-Aminopyridine - pharmacology Animals Dose-Response Relationship, Drug Female Health aspects Large-Conductance Calcium-Activated Potassium Channels - metabolism Large-Conductance Calcium-Activated Potassium Channels - physiology Male Mice Mice, Inbred C57BL Myometrium Myometrium - drug effects Physiological aspects Potassium channels Potassium Channels, Voltage-Gated - metabolism Potassium Channels, Voltage-Gated - physiology Pregnancy Pregnancy, Animal Shal Potassium Channels - metabolism Shal Potassium Channels - physiology Uterine Contraction - metabolism Uterine Contraction - physiology Uterus United States
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Summary:	Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv) channels and large-conductance, calcium-activated potassium (BK) channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. The Kv channel blocker 4-aminopyridine (4-AP) caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar) but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were found in isolated myometrium from both nonpregnant and term-pregnant mice, and one of these proteins - Kv4.3 - was found to disappear in term-pregnant tissues. These findings suggest a role for Kv channels in the regulation of uterine contractility, and that changes in the expression and/or function of specific Kv channels may account for the functional changes seen in pregnant myometrium.
ISSN:	1477-7827 1477-7827
DOI:	10.1186/1477-7827-5-41