Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cells

Authors: Wong K-L.¹; Chan P.¹; Huang W-C.²; Yang T-L.²; Liu I-M.³; Lai T-Y.⁴; Tsai C-C.⁴; Cheng J-T.²

Source: Clinical and Experimental Pharmacology and Physiology, Volume 30, Number 10, October 2003 , pp. 793-798(6)

Publisher: Wiley-Blackwell

Abstract:

Summary

1. Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders.

2. In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ([Ca²⁺]_i) was investigated in cultured vascular smooth muscle (A7r5) cells using the Ca²⁺-sensitive dye Fura-2 as an indicator.

3. The increase in [Ca²⁺]_i in A7r5 cells produced by vasopressin (1 µmol/L) or phenylephrine (1 µmol/L) was attenuated by TMP in a concentration-dependent manner. Only inhibitors specific to ATP-sensitive potassium (K_ATP) channels or small conductance calcium-activated potassium (SK_Ca) channels attenuated the action of TMP (10 µmol/L) on [Ca²⁺]_i. However, blockers of other K⁺ channels failed to modify the inhibitory action of TMP (10 µmol/L) on [Ca²⁺]_i.

4. The action of TMP on membrane potential in A7r5 cells was monitored by the fluorescence of bisoxonol. Tetramethylpyrazine caused a concentration-dependent inhibition of changes in membrane potential elicited by KCl (20 mmol/L) or phenylephrine (1 µmol/L), an effect that was totally reversed by glibenclamide (100 µmol/L) and apamin (100 nmol/L) in combination.

5. The results obtained indicate that the decrease in [Ca²⁺]_i in A7r5 cells produced by TMP is mediated mainly by opening of K_ATP and/or SK_Ca channels.

Keywords: bisoxonol; cultured vascular smooth muscle cells; Fura-2; intracellular calcium concentrations; potassium channel blockers; tetramethylpyrazine

Document Type: Research article

DOI: http://dx.doi.org/10.1046/j.1440-1681.2003.03913.x

Affiliations: 1: Divison of Cardiovascular Medicine, Graduate Institute of Medical Sciences, Taipei Medical University and affiliated Taipei Wan-Fang Hospital, Taipei City, 2: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, 3: Department of Pharmacy, Tajen Institute of Technology, Yen-Pou, Ping Tung Shien and 4: Department of Traditional Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical College, Taichung City, Taiwan

Publication date: 2003-10-01

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