title: Inhibitory effect of cinobufagin on L-type Ca2+ currents, contractility, and Ca2+ homeostasis of isolated adult rat ventricular myocytes.
abstract: Cinobufagin (CBG), a major bioactive ingredient of the bufanolide steroid compounds of Chan Su, has been widely used to treat coronary heart disease. At present, the effect of CBG on the L-type Ca(2+) current (I Ca-L) of ventricular myocytes remains undefined. The aim of the present study was to characterize the effect of CBG on intracellular Ca(2+) ([Ca(2+)]i) handling and cell contractility in rat ventricular myocytes. CBG was investigated by determining its influence on I Ca-L, Ca(2+) transient, and contractility in rat ventricular myocytes using the whole-cell patch-clamp technique and video-based edge-detection and dual-excitation fluorescence photomultiplier systems. The dose of CBG (10(-8) M) decreased the maximal inhibition of CBG by 47.93%. CBG reduced I Ca-L in a concentration-dependent manner with an IC50 of 4 × 10(-10) M, upshifted the current-voltage curve of I Ca-L, and shifted the activation and inactivation curves of I Ca-L leftward. Moreover, CBG diminished the amplitude of the cell shortening and Ca(2+) transients with a decrease in the time to peak (Tp) and the time to 50% of the baseline (Tr). CBG inhibited L-type Ca(2+) channels, and reduced [Ca(2+)]i and contractility in adult rat ventricular myocytes. These findings contribute to the understanding of the cardioprotective efficacy of CBG.
authors: Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, China.
authors: Pinya
authors: P
authors: Li
authors: Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, China.
authors: Qiongtao
authors: Q
authors: Song
authors: Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, China.
authors: Tao
authors: T
authors: Liu
authors: The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors: Zhonglin
authors: Z
authors: Wu
authors: The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors: Xi
authors: X
authors: Chu
authors: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China.
authors: Xuan
authors: X
authors: Zhang
authors: Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, China ; Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China.
authors: Ying
authors: Y
authors: Zhang
authors: Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, China ; Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China.
authors: Yonggang
authors: Y
authors: Gao
authors: Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, China ; Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China.
authors: Jianping
authors: J
authors: Zhang
authors: Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, China ; Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China.
authors: Li
authors: L
authors: Chu
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D002478:Cells, Cultured; D056966:Excitation Contraction Coupling / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology*
chemical_list: D002018:Bufanolides; D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D002118:Calcium; C002471:cinobufagin