title: Activation of KCNQ channels located on the skeletal muscle membrane by retigabine and its influence on the maximal muscle force in rat muscle strips.
abstract: Retigabine is a new antiepileptic drug with the main mechanism of action: activation of voltage-gated potassium channels (Kv7) represented in many tissues including the excitable cells-neuronal and muscular. The aim of this article is to determine the role of potassium channels located on the skeletal muscle membrane in the in vivo and in vitro reduction of muscle contractile activity induced by retigabine. We studied the effects of retigabine on the motor function in vivo using a bar holding test and exploratory activity using open field test in rats. Electrical field stimulation (EFS) was applied to skeletal muscle strips in vitro in order to evaluate muscular activity. We registered a significant decrease in the muscle tone and exploratory activity of rats, treated orally with 60 mg/kg bw retigabine. In vitro experiments showed decrease in the maximal muscle force of strips in the presence of retigabine in the medium after both indirect (nerve-like) and direct (muscle-like) stimulation. The effects were fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the relation between these types of potassium channels and the observed change in the muscle force. Based on these results, we can conclude that skeletal muscle Kv7 channels play a significant role in the myorelaxation and reduced muscle force registered after treatment with Kv7 channels openers (e.g., retigabine). The hyperpolarization of skeletal muscle membrane caused by accelerated K(+) efflux may be the underlying cause for the effect of retigabine on the muscle tone.
authors.affiliation: Department of Biophysics, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4000, Plovdiv, Bulgaria.
authors.forename: P
authors.initials: P
authors.lastname: Zagorchev
authors.affiliation: Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4000, Plovdiv, Bulgaria. apostolova1212@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Apostolova
authors.affiliation: Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4000, Plovdiv, Bulgaria.
authors.forename: V
authors.initials: V
authors.lastname: Kokova
authors.affiliation: Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4000, Plovdiv, Bulgaria.
authors.forename: L
authors.initials: L
authors.lastname: Peychev
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D051656:KCNQ Potassium Channels / Q000819:agonists* / Q000378:metabolism; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D009119:Muscle Contraction; D009126:Muscle Relaxation / Q000187:drug effects*; D053580:Muscle Strength / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D010655:Phenylenediamines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017208:Rats, Wistar
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; D051656:KCNQ Potassium Channels; D049990:Membrane Transport Modulators; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; C101866:ezogabine
keywords: KCNQ; Maximal muscle force; Rats; Retigabine; Striated muscle
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4333-8
references.pmid: 10760300
references.citation: Br J Pharmacol. 2003 Sep;140(1):159-69
references.pmid: 12967945
references.citation: Pharmacol Rep. 2010 Mar-Apr;62(2):211-9
references.pmid: 20508276
references.citation: Front Biosci. 2007 Jan 01;12:174-91
references.pmid: 17127292
references.citation: Epilepsy Res. 1996 Apr;23(3):211-23
references.pmid: 8739124
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11492-6
references.pmid: 7972090
references.citation: Eur J Pharmacol. 2014 Jun 15;733:97-101
references.pmid: 24726846
references.citation: Br J Pharmacol. 2013 Jul;169(6):1290-304
references.pmid: 23586426
references.citation: Evid Based Complement Alternat Med. 2012;2012:803082
references.pmid: 22536291
references.citation: Int J Dev Neurosci. 2009 Apr;27(2):149-55
references.pmid: 19103275
references.citation: J Neurophysiol. 2006 Aug;96(2):535-43
references.pmid: 16394077
references.citation: J Pharmacol Exp Ther. 2010 Mar;332(3):811-20
references.pmid: 20040580
references.citation: Neurotherapeutics. 2007 Jan;4(1):149-54
references.pmid: 17199031
references.citation: J Cell Sci. 2012 May 1;125(Pt 9):2105-14
references.pmid: 22627029
references.citation: Br J Pharmacol. 2009 Apr;156(8):1196-203
references.pmid: 19751313
references.citation: Eur J Pharmacol. 2014 Mar 5;726:133-7
references.pmid: 24457124
references.citation: J Anesth. 2016 Feb;30(1):109-15
references.pmid: 26302692
references.citation: J Physiol. 1991 Jan;432:259-82
references.pmid: 1886057
references.citation: Mol Pain. 2014 Feb 21;10:15
references.pmid: 24555569
references.citation: Molecules. 2011 Aug 16;16(8):7019-42
references.pmid: 21847072
references.citation: Epilepsy Res. 2013 Mar;104(1-2):84-93
references.pmid: 22999391
references.citation: Heart Rhythm. 2013 May;10(5):726-7
references.pmid: 23416379
references.citation: Am J Physiol Heart Circ Physiol. 2015 Aug 1;309(3):H481-9
references.pmid: 26055791
references.citation: Clin Ther. 2012 Sep;34(9):1845-56.e1
references.pmid: 22917854
references.citation: J Biomed Biotechnol. 2010;2010:459789
references.pmid: 20379364
references.citation: Epilepsia. 2012 Mar;53(3):425-36
references.pmid: 22221318
references.citation: Epilepsy Res. 1994 Feb;17(2):95-134
references.pmid: 8194514
references.citation: ASN Neuro. 2015 Mar 24;7(2):null
references.pmid: 25810356
references.citation: PLoS One. 2013 Sep 20;8(9):e75875
references.pmid: 24073284
references.citation: Behav Brain Res. 2005 May 7;160(1):99-106
references.pmid: 15836904