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Effect of mexiletine on long QT syndrome model
Hong-Wei Wang1, Yan-Qian Zheng, Zhi-Fang Yang
1Department of Physiology, Shanghai Second Medical University, Shanghai 200025, China.
Aim:
To make a LQT3 model (one form of the long QT syndromes) and to investigate the effect of mexiletine on LQT3.
Methods:
Sea anemone toxin (ATX II) was used to produce the LQT3 model. The Effect of mexiletine on LQT3 was performed on single Na channel, action potential, and electrocardiography in guinea pigs.
Results:
With the binding of ATX II to the Na+ channels, the probability of being in the open state and the open time constant of single Na+ channel with long opening mode increased significantly. Action potential duration APD50, APD90, and the maximal upstroke velocity of phase 0 were increased by 25.8 %, 26.1 %, and 12 %, respectively. The QT interval and QTc, a rectified QT interval, increased by 12.8 % and 16.9 %. On the contrary, after application of mexiletine, the open probability of single Na+ channel was reduced greatly. In the presence of ATX II (40 nmol/L), mexiletine (1, 5, 15, 45, 70 micromol/L) shortened the APD50 by 0.5 %, 6.7 %, 14.4 %, 19.4 %, and 18.8 %, respectively, and decreased the APD90 and Vmax accordingly. In the experiments with ECG, mexiletine reversed the ATX II-produced prolongation effects on QTc in a dose-dependent manner.
Conclusion:
Mexiletine may be an effective drug in the treatment of LQT3.