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http://dx.doi.org/10.4196/kjpp.2020.24.6.503

The agonistic action of URO-K10 on Kv7.4 and 7.5 channels is attenuated by co-expression of KCNE4 ancillary subunit  

Lee, Jung Eun (Department of Physiology, Seoul National University College of Medicine)
Park, Christine Haewon (Department of Physiology, Seoul National University College of Medicine)
Kang, Hana (Department of Physiology, Seoul National University College of Medicine)
Ko, Juyeon (Department of Physiology, Seoul National University College of Medicine)
Cho, Suhan (Department of Physiology, Seoul National University College of Medicine)
Woo, JooHan (Department of Physiology, Dongguk University College of Medicine)
Chae, Mee Ree (Department of Urology, Samsung Medical Center)
Lee, Sung Won (Department of Urology, Samsung Medical Center)
Kim, Sung Joon (Department of Physiology, Seoul National University College of Medicine)
Kim, Jinsung (Department of Physiology, Seoul National University College of Medicine)
So, Insuk (Department of Physiology, Seoul National University College of Medicine)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.24, no.6, 2020 , pp. 503-516 More about this Journal
Abstract
KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50, the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the β ancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQ-specific agonist in the tissue.
Keywords
KCNE4; KCNQ4; KCNQ5; Vasorelaxation;
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