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

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.