Mechanism of osthole inhibition of vascular Ca(v)1.2 current

European Journal of Pharmacology
Fabio FusiSimona Saponara

Abstract

Osthole is a coumarin extracted from Cnidium monnieri (L.) Cusson. The medicinal plant is widely used in Vietnamese as well as Chinese traditional medicine as a vasodilating and antihypertensive agent. Here we have tested the proposition that the block of Ca(v)1.2 channels is mainly responsible for its vascular activity. An in-depth analysis of the effect of osthole on Ca(v)1.2 current (I(Ca1.2)) was performed in rat tail artery myocytes using the whole-cell patch-clamp method. Osthole decreased I(Ca1.2) in a concentration- and voltage-dependent manner. At holding potentials of -50 and -80mV, the pIC(50) values were 4.78±0.07 and 4.36±0.08, respectively; the latter corresponded to the drug apparent dissociation constant for resting channels, K(R), of 47.8μM. Osthole speeded up the inactivation kinetics of I(Ca1.2) and shifted the voltage dependence of the inactivation curve to more negative potentials in a concentration-dependent manner, with an apparent dissociation constant for inactivated channels (K(I)) of 6.88μM. Block of I(Ca1.2) was frequency-dependent and the rate of recovery from inactivation was slowed down. In conclusion, osthole is a vascular Ca(v)1.2 channel antagonist stabilizing the channel in its inactivated sta...Continue Reading

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Citations

Apr 4, 2014·Biological & Pharmaceutical Bulletin·Nguyen Manh CuongFabio Fusi
Aug 6, 2015·The American Journal of Chinese Medicine·Yi-Min LiLu-Ping Qin
Aug 8, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Zhong-Rong ZhangChun Wai Chan
Jun 12, 2013·European Journal of Pharmacology·Fabio FusiNguyen Hai Nam
Dec 29, 2018·Beilstein Journal of Organic Chemistry·Christiane Schultze, Bernd Schmidt
Aug 22, 2020·Investigative Ophthalmology & Visual Science·Yuchen FanTao Guo
May 18, 2013·Journal of Asian Natural Products Research·Xiu-Lan XinXiao-Bo Wang
Feb 9, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hanan KhairyMohamed-Assem S Marie

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