Acta Pharmacologica Sinica (2010) 31: 297–306; doi: 10.1038/aps.2010.8; published online 22 February 2010

Cardio-Electrophysiological Research Laboratory, Medical College of Wuhan University of Science and Technology, Wuhan 430081, China

Aim: To investigate the blocking effects of methylflavonolamine (MFA) on human Na_V1.5 channels expressed in Xenopus laevis oocytes and on sodium currents (I_Na) in rabbit ventricular myocytes.

Methods: Human Na_V1.5 channels were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp technique.  I_Na and action potentials in rabbit ventricular myocytes were studied using the whole-cell recording.

Results: MFA and lidocaine inhibited human Na_V1.5 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 I_Na toward more positive potentials, shifted the steady-state inactivation curve of I_Na toward more negative potentials and postponed the recovery of the I_Na inactivation state.  In rabbit ventricular myocytes, MFA inhibited I_Na with a shift in the steady-state inactivation curve toward more negative potentials, thereby postponing the recovery of the I_Na 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 (V_max) 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.

Keywords: methylflavonolamine; lidocaine; sodium channel; Xenopus oocytes; ventricular myocytes