Effects Of Tetramethylpyrazine On Ionic Currents In Guinea Pig Ventricular Myocytes

The ligustrazine, an active ingredient of a medicinal plant in China (ligustium Wollichii Franchat) has been identified as tetramethylpyrazine (IMP). It elicited vasodilatation and was known to potentiate the cardiac contraction and inhibit platelet aggregation. It was used to clinically treat occlusive cerebral arteriolar disease. It has been reported that IMP could potentiate the force of contraction and increase the action potential duration. Similar effencts were also observable in slow action potential, and they could be antagonized by verapamil. Thus, these effects of IMP could probably be related to the increase of the calcium current.In the present study of the mechanism of ionic channelmodulation by IMP, we have investigated its effects on ionic currents by use of the whole-cell patch clamp technique. Single ventricular cells of guinea pig were isolated with a collagenase (I-type) dispersion method, and the ionic basis underlying the effect of IMP was studied at different voltage-clamp protocols. The results are as follows:1. IMP increased the current amplitude of lCa,L in a dose-dependent manner and the increase of ICa,L is not accompanied by significant shifts in the current-voltage relationships. It still reached maximum at 0~+10 mV. 0. 3 mmol L~' TMP increased the peak current amplitude of IG,,I. from 9. 14 + 1. 87pA/pF to 10. 12 + 2. 24 pA/pF (n=3, P<0. 05) , 1 mmol L' TMP increased the peak current amplitude from 13. 42 + 2. 41pA/pF to 15.96 + 2.98 pA/pF (n = 7, P<0.05 )0 3 mmol L1 TMP increased the peak current amplitude from 7. 15 + 0. 65pA/pF to 11. 39 + 0. 99pA/pF (n=6, P<0. 01 )0 TMP 0.3, K 3 mmol U1 markedly increased LCa, L by 9.8% + 4.3%, 20. 0%+5. 0%, 60. 2%+6. 0%,respectively.2. TMP increased only the inward component and had no significant effect on the outward component of IK!. For the inward component, TMP increased the peak IKi from 30.76 + 5. 42pA/pF to 45. 10 + 5.98pA/pF (n=5, P<0. 001) at -170mVand the maximal slope conductance from 0.31+0.01 nS/pF to 0.44 + 0.14 nS/pF (n=5, P<0. 01) . For the outward component, TMP changed the peak IK1 from 4 . 33 + 0. 65 pA/pF to 4. 02+0. 52 pA/pF(n=5, P=NS) at -40 mV.Conclusion: TMP increases L - type Ca2+ current in a dose-dependent manner, increased the inward component of IK1 , but has no significant effect on the outward component of IK1.