title: Effects of total flavones from Acanthopanax senticosus on L-type calcium channels, calcium transient and contractility in rat ventricular myocytes.
abstract: Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal medicine, has been widely used to treat ischemic heart disease. However, the underlying cellular mechanisms of its benefits to cardiac function remain unclear. The present study examined the effects of total flavones from AS (TFAS) on L-type Ca(2+) channel currents (ICa-L ) using the whole cell patch-clamp technique and on intracellular calcium ([Ca(2+) ]i ) handling and cell contractility in rat ventricular myocytes with the aid of a video-based edge-detection system. Exposure to TFAS resulted in a concentration- and voltage-dependent blockade of ICa-L , with the half-maximal inhibitory concentration (IC50 ) of 283.12 µg/mL and the maximal inhibitory effect of 36.49 ± 1.95%. Moreover, TFAS not only increased the maximum current in the current-voltage relationship but also shifted the activation and inactivation curves of ICa-L toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced amplitudes of myocyte shortening and [Ca(2+) ]i with an increase in the time to 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of TFAS may be attributed mainly to the attenuation of [Ca(2+) ]i through the direct inhibition of ICa-L in rat ventricular myocytes and consequent negative effect on myocardial contractility.
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, Hebei, China; Department of Pharmacy, The Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, Hebei, China.
authors.forename: Shengjiang
authors.initials: S
authors.lastname: Guan
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Ma
authors.forename: Xi
authors.initials: X
authors.lastname: Chu
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Gao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zhang
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Liu
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Chu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D028001:Eleutherococcus / Q000737:chemistry*; D047309:Flavones / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D047309:Flavones; D002118:Calcium
keywords: L-type calcium channel; calcium overload; calcium transient; myocyte shortening; patch clamp; total flavones