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A role for voltage‐gated, but not Ca 2+ ‐activated, K + channels in regulating spontaneous contractile activity in myometrium from virgin and pregnant rats
Author(s) -
Aaronson Philip Irving,
Sarwar Uzma,
Gin Stephanie,
Rockenbauch Uli,
Connolly Michelle,
Tillet Alexandra,
Watson Sarah,
Liu Bing,
Tribe Rachel Marie
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706644
Subject(s) - myometrium , iberiotoxin , endocrinology , medicine , contractility , tetraethylammonium , phentolamine , chemistry , muscle contraction , contraction (grammar) , bk channel , uterine contraction , potassium channel , propranolol , uterus , potassium , organic chemistry
The roles of voltage‐gated ( K V ) and large conductance Ca 2+ ‐activated K + (BK Ca ) channels in regulating basal contractility in myometrial smooth muscle are unresolved. The aim of this study was to determine the effects of inhibition of these channels on spontaneous rhythmic contraction in myometrial strips from four groups of rats: nonpregnant and during early (day 7), mid‐ (day 14), and late (day 21) pregnancy. BK Ca channels were inhibited using iberiotoxin (1–100 n M ), paxilline (1–10 μ M ) or penitrem A (1–500, or 3000 n M ); K V channels were inhibited using tetraethylammonium (TEA; 1–10 m M ) and/or 4‐aminopyridine (4‐AP; 1–5 m M ). Contractility was assessed as mean integral tension (MIT). Time/vehicle controls were also performed. None of the selective BK Ca channel inhibitors significantly affected contractility in myometrial strips from either nonpregnant or pregnant animals. 4‐AP caused concentration‐dependent increases in MIT in myometrium in all four groups. TEA (5 and 10 m M ) significantly increased MIT in myometrium from nonpregnant, and mid‐ and late pregnant rats, but not in myometrium from early pregnant rats. TEA and 4‐AP still caused an increase in MIT following treatment with 3000 n M penitrem A or a combination of propranolol, phentolamine, atropine (all 1 μ M ) and capsaicin (10 μ M ) in myometrial strips from nonpregnant rats. These results indicate that whereas BK Ca channels play little or no part in controlling basal rhythmicity in rat myometrium, K V channels appear to play a crucial role in this regard, especially during mid‐ and late pregnancy.British Journal of Pharmacology (2006) 147 , 815–824. doi: 10.1038/sj.bjp.0706644