Blocking effect of methylflavonolamine on human NaV1.5 channels expressed in Xenopus laevis oocytes and on sodium currents in rabbit ventricular myocytes  

作　　者：Xin-rong FAN Ji-hua MA Pei-hua ZHANG Jun-lian XING 

机构地区：[1]Cardio-Electrophysiological Research Laboratory, Medical College of Wuhan University of Science and Technology, Wuhan 430081, China

出　　处：《Acta Pharmacologica Sinica》2010年第3期297-306,共10页中国药理学报（英文版）

摘　　要：Aim： To investigate the blocking effects of methylflavonolamine （MFA） on human NaV1.5 channels expressed in Xenopus laevis oocytes and on sodium currents （INa） in rabbit ventricular myocytes.Methods： Human NaV1.5 channels were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp technique. INa and action potentials in rabbit ventricular myocytes were studied using the whole-cell recording.Results： MFA and lidocaine inhibited human NaV1.5 channels expressed in Xenopus oocytes in a positive rate-dependent and concentration-dependent manner, with IC50 values of 72.61 μmol/L and 145.62 μmol/L, respectively. Both of them markedly shifted the steady-state activation curve of INa toward more positive potentials, shifted the steady-state inactivation curve of INa toward more negative potentials and postponed the recovery of the INa inactivation state. In rabbit ventricular myocytes, MFA inhibited INa with a shift in the steady-state inactivation curve toward more negative potentials, thereby postponing the recovery of the INa inactivation state. This shift was in a positive rate-dependent manner. Under current-clamp mode, MAF significantly decreased action potential amplitude （APA） and maximal depolarization velocity （Vmax） and shortened action potential duration （APD）, but did not alter the resting membrane potential （RMP）. The demonstrated that the kinetics of sodium channel blockage by MFA resemble those of class I antiarrhythmic agents such as lidocaine.Conclusion： MFA protects the heart against arrhythmias by its block ing effect on sodium channels.

关 键 词：methylflavonolamine LIDOCAINE sodium channel Xenopus oocytes ventricular myocytes 

分 类 号：Q424[生物学—神经生物学] Q463[生物学—生理学]