Premium
Loss of functional K + channels encoded by ether‐à‐go‐go‐related genes in mouse myometrium prior to labour onset
Author(s) -
Greenwood I. A.,
Yeung S. Y.,
Tribe R. M.,
Ohya S.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.171272
Subject(s) - myometrium , contractility , myocyte , medicine , erg , endocrinology , gene isoform , gene expression , biology , chemistry , microbiology and biotechnology , gene , uterus , biochemistry , neuroscience , retina
There is a growing appreciation that ion channels encoded by the ether‐à‐go‐go‐related gene family have a functional impact in smooth muscle in addition to their accepted role in cardiac myocytes and neurones. This study aimed to assess the expression of ERG1–3 (KCNH1–3) genes in the murine myometrium (smooth muscle layer of the uterus) and determine the functional impact of the ion channels encoded by these genes in pregnant and non‐pregnant animals. Quantitative RT‐PCR did not detect message for ERG2 and 3 in whole myometrial tissue extracts. In contrast, message for two isoforms of mERG1 were readily detected with mERG1a more abundant than mERG1b. In isometric tension studies of non‐pregnant myometrium, the ERG channel blockers dofetilide (1 μ m ), E4031 (1 μ m ) and Be‐KM1 (100 n m ) increased spontaneous contractility and ERG activators (PD118057 and NS1643) inhibited spontaneous contractility. In contrast, neither ERG blockade nor activation had any effect on the inherent contractility in myometrium from late pregnant (19 days gestation) animals. Moreover, dofetilide‐sensitive K + currents with distinctive ‘hooked’ kinetics were considerably smaller in uterine myocytes from late pregnant compared to non‐pregnant animals. Expression of mERG1 isoforms did not alter throughout gestation or upon delivery, but the expression of genes encoding auxillary subunits (KCNE) were up‐regulated considerably. This study provides the first evidence for a regulation of ERG‐encoded K + channels as a precursor to late pregnancy physiological activity.