The effect of ligustrazine on L-type calcium current, calcium transient and contractility in rabbit ventricular myocytes.
BACKGROUND
Ligustrazine, the biologically active ingredient isolated from a popular Chinese medicinal plant, Ligusticum chuanxiong Hort. (Umbelliferae), has been used effectively to treat ischemic heart diseases, cerebrovascular and thrombotic vascular diseases since the 1970s.


METHODS
At present, the effect of ligustrazine on L-type calcium current (I(Ca-L)) of ventricular myocytes remains controversial. In this study, we use the whole-cell patch-clamp techniques and video-based edge detection and dual excitation fluorescence photomultiplier systems to study the effects of ligustrazine on I(Ca-L), and calcium transient and contractility in rabbit ventricular myocytes in the absence and presence of isoprenaline (ISO).


RESULTS
Ligustrazine (5 μM) in low concentration did not affect I(Ca-L) (P>0.05), higher concentrations of this drug (10, 20, 40, 80 μM) inhibited I(Ca-L) in a concentration-dependent manner and reduced I(Ca-L) by 9.6 ± 2.9%, 21.0 ± 4.3%, 33.9 ± 4.3%, and 51.6 ± 7.3%, respectively. Under normal conditions, ligustrazine (40 μΜ) reduced baseline of fura-2 fluorescence intensities (FFI, 340/380 ratio), namely diastolic calcium concentration, changes in FFI (ΔFFI, 340/380 ratio) and maximal velocity of Ca(2+) rise and decay (340/380 ratio/ms) by 6.3%, 26.1%, 25.2%, and 26.5%, and decreased sarcomere peak shorting (PS) and maximal velocity of shorting and relengthening by 36.4%, 31.9%, and 25.0%, respectively. Similarly, ligustrazine (40 μM) reduced baseline FFI, ΔFFI, and maximal velocity of Ca(2+) rise and decay by 14.1%, 51.1%, 35.2%, and 41.1%, and reduced sarcomere PS and maximal velocity of shorting and relengthening by 38.6%, 50.0% and 39.1%, respectively, in the presence of ISO.


CONCLUSIONS
Ligustrazine not only significantly inhibits I(Ca-L) in a concentration-dependent manner but also suppressed calcium transient and contraction in the absence and presence of ISO.
Cardio-Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China.
Zhiqiang
Z
Ren
Jihua
J
Ma
Peihua
P
Zhang
Antao
A
Luo
Shuo
S
Zhang
Linghao
L
Kong
Chunping
C
Qian
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D011719:Pyrazines / Q000494:pharmacology*; D011817:Rabbits; D013566:Sympathomimetics / Q000494:pharmacology; D016276:Ventricular Function / Q000187:drug effects
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011719:Pyrazines; D013566:Sympathomimetics; D007545:Isoproterenol; D002118:Calcium; C017953:tetramethylpyrazine