Activation of KCNQ channels located on the skeletal muscle membrane by retigabine and its influence on the maximal muscle force in rat muscle strips

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2016-04, Vol.389 (4), p.439-446
• Main Authors: Zagorchev, P., Apostolova, E., Kokova, V., Peychev, L.
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants - pharmacology; Biomedical and Life Sciences; Biomedicine; Carbamates - pharmacology; Dose-Response Relationship, Drug; Electric Stimulation; In Vitro Techniques; KCNQ Potassium Channels - agonists; KCNQ Potassium Channels - metabolism; Male; Membrane Transport Modulators - pharmacology; Muscle Contraction; Muscle Relaxation - drug effects; Muscle Strength - drug effects; Muscle, Skeletal - drug effects; Muscle, Skeletal - innervation; Muscle, Skeletal - metabolism; Neurosciences; Original Article; Pharmacology/Toxicology; Phenylenediamines - pharmacology; Potassium Channel Blockers - pharmacology; Rats, Wistar
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-016-1211-0

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.