Quinidine Depresses the Transmural Electrical Heterogeneity of Transient Outward Potassium Current of the Right Ventricular Outflow Tract Free Wall

BACKGROUND#ENTITYSTARTX02014;: Electrical heterogeneity of the right ventricular outflow tract (RVOT) is regarded as one of the main electrophysiological substrates for Brugada syndrome. Recently quinidine has shown efficacy in patients with Brugada syndrome due to its ability to inhibit potassium current especially 4-aminopyridine-sensitive, non-Ca(2+) -dependent transient outward potassium current (Ito). However, much less is known on how extent quinidine in clinical therapeutic concentration range can inhibit this kind of electrical heterogeneity of RVOT Ito. METHODS AND RESULTS#ENTITYSTARTX02014;: Single RVOT free wall epicardial (Epi) cell, midmyocardial (M) cell and endocarcial (Endo) cells were used for whole-cell voltage clamping and Ito was recorded at 37°C, 0.2 Hz depolarization pulse. Evident Ito tranmural heterogeneity existed in RVOT free wall. Under the condition of baseline, of 10 μM quinidine perfusion 5 minutes (mins), and of 10 μM quinidine perfusion 7-10 mins, from 0 mV to 70 mV the whole transmural average Ito values of RVOT free wall were 10.2 pA/pF, 5.5 pA/pF and 3.5 pA/pF, respectively (between groups, P< 0.01). The inhibitory percentage of 10 μM quinidine at 5 mins and 7-10 mins steady-state level on the the whole Ito transmural heterogeneity of RVOT free wall were 46.3%±6% and 66.5%±11%, respectively. CONCLUSIONS#ENTITYSTARTX02014;: There exists a robust Ito transmural electrical heterogeneity in RVOT free wall and quinidine in clinical therapeutic concentration can depress this kind of heterogeneity effectively.