The Ca(2+) channel inhibitor efonidipine decreases voltage-dependent K(+) channel activity in rabbit coronary arterial smooth muscle cells

Mi-Hyeong Park; Youn Kyoung Son; Da Hye Hong; Il-Whan Choi; Dae-Joong Kim; Haena Lee; Hyoweon Bang; Sung Hun Na; Hongliang Li; Su-Hyun Jo; Won Sun Park

doi:10.1016/j.vph.2013.07.005

The Ca(2+) channel inhibitor efonidipine decreases voltage-dependent K(+) channel activity in rabbit coronary arterial smooth muscle cells

Vascul Pharmacol. 2013 Sep-Oct;59(3-4):90-5. doi: 10.1016/j.vph.2013.07.005. Epub 2013 Jul 19.

Authors

Mi-Hyeong Park¹, Youn Kyoung Son, Da Hye Hong, Il-Whan Choi, Dae-Joong Kim, Haena Lee, Hyoweon Bang, Sung Hun Na, Hongliang Li, Su-Hyun Jo, Won Sun Park

Affiliation

¹ Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.

PMID: 23876554
DOI: 10.1016/j.vph.2013.07.005

Abstract

The effect of efonidipine, a commercially available antihypertensive drug and Ca(2+) channel inhibitor, on voltage-dependent K(+) (Kv) channels was studied in freshly isolated rabbit coronary arterial smooth muscle cells using the whole-cell patch clamp technique. The amplitude of Kv current was decreased by application of efonidipine in a dose-dependent manner, with IC50 of 0.26μM and a Hill coefficient of 0.91, which suggests 1:1 binding stoichiometry. Efonidipine did not affect voltage-dependent activation of the Kv channel, but shifted the inactivation curve by -8.87mV. The inhibitory effect of efonidipine was not significantly changed by depletion of extracellular Ca(2+) or intracellular ATP, which indicated no involvement of the Ca(2+) channel or intracellular protein kinase-dependent cascades. We conclude that efonidipine dose-dependently inhibits Kv current in a phosphorylation- and Ca(2+) channel-independent manner.

Keywords: Coronary artery; Efonidipine; Voltage-dependent K(+) channels.

Publication types

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

MeSH terms

Animals
Antihypertensive Agents / administration & dosage
Antihypertensive Agents / pharmacology
Calcium Channel Blockers / administration & dosage
Calcium Channel Blockers / pharmacology*
Coronary Vessels / drug effects
Coronary Vessels / metabolism
Dihydropyridines / administration & dosage
Dihydropyridines / pharmacology*
Dose-Response Relationship, Drug
Inhibitory Concentration 50
Muscle, Smooth, Vascular / cytology
Muscle, Smooth, Vascular / drug effects
Muscle, Smooth, Vascular / metabolism
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / metabolism
Nitrophenols / administration & dosage
Nitrophenols / pharmacology*
Organophosphorus Compounds / administration & dosage
Organophosphorus Compounds / pharmacology
Patch-Clamp Techniques
Phosphorylation
Potassium Channel Blockers / administration & dosage
Potassium Channel Blockers / pharmacology*
Potassium Channels, Voltage-Gated / drug effects*
Potassium Channels, Voltage-Gated / metabolism
Rabbits

Substances

Antihypertensive Agents
Calcium Channel Blockers
Dihydropyridines
Nitrophenols
Organophosphorus Compounds
Potassium Channel Blockers
Potassium Channels, Voltage-Gated
efonidipine