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

Aim: To investigate the blocking effects of methylflavonolamine (MFA) on human Na(V)1.5 channels expressed in Xenopus laevis oocytes and on sodium currents (I-Na) in rabbit ventricular myocytes. Methods: Human Na(V)1.5 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(V)1.5 channels expressed in Xenopus oocytes in a positive rate-dependent and concentration-dependent manner, with IC50 values of 72.61 mu mol/L and 145.62 mu mol/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 blocking effect on sodium channels.