Comptes rendus de l’Acade'mie bulgare des Sciences, Vol 71, No10, pp.1428-1438

Activation of Kv7.2 to Kv7.5 Channels by Retigabine Modulates the Effects of Histamine and 2‑(2‑Pyridyl) Ethylamine on Smooth Muscles

Plamen Zagorchev, Elisaveta Apostolova, Vesela Kokova, Lyudmil Peychev, Zhivko Peychev, Milena Draganova-Filipova


Retigabine is an antiepileptic drug whose main mechanism of action involves opening of voltage-gated potassium channels (Kv7.2‑Kv7.5). The aim of this study is to evaluate the effect of retigabine on the cell response to histamine and H1 receptor agonist 2‑(2‑Pyridyl) ethylamine. We examined the effect of 10 µM histamine and 10 µM 2‑(2‑Pyridyl) ethylamine on spontaneous smooth muscle contraction of guinea pig gastric corpus strips before and after 20‑min treatment with 2 µM retigabine. The effect of 10 µM histamine on the spontaneous smooth muscle contractility was diminished after treatment with 2 µM retigabine. Similar results were observed with 2‑(2‑Pyridyl) ethylamine (H1 receptor agonist). Activation of Kv7.2 to Kv7.5 channels by retigabine may lead to membrane hyperpolarization and may result in attenuated effects of histamine and 2‑(2‑Pyridyl) ethylamine on smooth muscles. A similar process could occur in the neurons, where Kv7 channels and H1 receptors are present.

Key words: membrane hyperpolarization, guinea pig corpus smooth muscle, spontaneous smooth muscle contraction

DOI: 10.7546/CRABS.2018.10.18