W-7 inhibits voltage-dependent K(+) channels independent of calmodulin activity in rabbit coronary arterial smooth muscle cells

Hongliang Li; Il-Whan Choi; Da Hye Hong; Youn Kyoung Son; Sung Hun Na; Won-Kyo Jung; Amy L Firth; In Duk Jung; Yeong-Min Park; Won Sun Park

doi:10.1016/j.ejphar.2014.12.026

W-7 inhibits voltage-dependent K(+) channels independent of calmodulin activity in rabbit coronary arterial smooth muscle cells

Eur J Pharmacol. 2015 Mar 5:750:14-9. doi: 10.1016/j.ejphar.2014.12.026. Epub 2015 Jan 22.

Authors

Hongliang Li¹, Il-Whan Choi², Da Hye Hong¹, Youn Kyoung Son¹, Sung Hun Na³, Won-Kyo Jung⁴, Amy L Firth⁵, In Duk Jung⁶, Yeong-Min Park⁷, Won Sun Park⁸

Affiliations

¹ Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
² Department of Microbiology, Inje University College of Medicine, Busan 614-735, South Korea.
³ Institute of Medical Sciences, Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
⁴ Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus) Pukyong National University, Busan 608-737, South Korea.
⁵ Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
⁶ Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701, South Korea.
⁷ Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701, South Korea. Electronic address: [email protected].
⁸ Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea. Electronic address: [email protected].

PMID: 25617796
DOI: 10.1016/j.ejphar.2014.12.026

Abstract

We investigated the effect of W-7, a calmodulin inhibitor, on voltage-dependent K(+) (Kv) channels in freshly isolated coronary arterial smooth muscle cells using the whole-cell patch clamp technique. The amplitude of Kv currents was inhibited by W-7 in a concentration-dependent manner, with an IC50 value of 3.38±0.47μM and a Hill coefficient of 0.84±0.10. W-7 shifted the activation curve to a more positive potential but had no significant effect on the inactivation curve, which indicated that W-7 inhibited the Kv current in a closed state of the Kv channel. Another calmodulin inhibitor, W-13, had no significant effect on Kv currents and did not change the inhibitory effect of W-7 on Kv channels. From these results, we conclude that W-7 inhibited the Kv current in a dose-dependent manner, but this inhibition occurred independent of calmodulin activity and in a closed (inactivated) state of the Kv channels.

Keywords: Coronary artery; Voltage-dependent K(+) channel; W-13 (CID:16760706); W-7; W-7 (CID:124887).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calmodulin / antagonists & inhibitors
Calmodulin / metabolism
Coronary Vessels / cytology*
Dose-Response Relationship, Drug
Electrophysiological Phenomena / drug effects
Inhibitory Concentration 50
Male
Muscle, Smooth, Vascular / cytology
Muscle, Smooth, Vascular / drug effects*
Muscle, Smooth, Vascular / metabolism*
Muscle, Smooth, Vascular / physiology
Potassium Channel Blockers / pharmacology*
Potassium Channels, Voltage-Gated / antagonists & inhibitors*
Potassium Channels, Voltage-Gated / metabolism
Rabbits
Sulfonamides / pharmacology*

Substances

Calmodulin
Potassium Channel Blockers
Potassium Channels, Voltage-Gated
Sulfonamides
W 7