The Antiarrhythmic Drug Flecainide Enhances Aversion to HCl in Mice

Flecainide enhances corda tympani (CT) nerve responses to HCl in mice. A, Representative examples of CT nerve responses to various taste solutions obtained after the intraperitoneal injection of vehicle (Ctrl, upper traces) or 2 mg/kg body weight flecainide (Fle, lower traces). B, CT nerve responses (normalized to that for 100 mm NH₄Cl) to sour [5 mm HCl; 30 mm acetic acid (AA); 10 mm citric acid (CA)], salty (100 mm NaCl; 100 mm KCl), sweet [300 mm sucrose (Suc)], bitter [20 mm quinine-HCl (QHCl)] and umami [100 mm monopotassium glutamate (MPG)] compounds recorded 15–30 min after the administration of vehicle (Ctrl, gray bars) or 2 mg/kg body weight flecainide (Fle, blue bars). Data are presented as the mean ± SD (n = 6–11). **p < 0.01 (unpaired t test). (C–G) Concentration-dependent responses to HCl (C) AA (D), CA (E), NaCl (F), and sucrose (G) obtained 15–30 min after the administration of vehicle (Ctrl, white symbols) or 2 mg/kg body weight flecainide (Fle, blue symbols). Data are presented as the mean ± SD (n = 4–11). *p < 0.05 (two-way ANOVA), ^†p < 0.01 (unpaired t test with Bonferroni correction). H, CT nerve responses (normalized to that for distilled water) to 100 mm NH₄Cl recorded 15–30 min after the administration of vehicle (Ctrl, gray bar) or 2 mg/kg body weight flecainide (Fle, blue bar). Data are presented as the mean ± SD (n = 11). p = 0.35 (unpaired t test), n.s. = no significance.

Long-term administration of flecainide enhances the behavioral responses of mice to HCl. Concentration-response relationships for varying concentrations of HCl (A), acetic acid (AA; B), and citric acid (CA; C), NaCl (D), NaCl + 30 μm amiloride (E), KCl (F), sucrose + 0.1 mm quinine-HCl (QHCl; G), QHCl (H) and monopotassium glutamate (MPG; I) obtained after daily intraperitoneal injections of vehicle (Ctrl, white symbols) or 2 mg/kg body weight flecainide (Fle, blue symbols) for 30 d. The lick ratio to distilled water is presented as the mean ± SD (n = 5). **p < 0.01 (two-way ANOVA).

Effects of flecainide on mouse taste bud cells. A, Expression of phospholipase C-β 2 (PLCβ2, a bitter/sweet/umami transduction molecule; magenta), and carbonic anhydrase-4 (CA4, a sour taste sensitive cell marker; green) in the circumvallate papillae after daily intraperitoneal injections of vehicle (Ctrl) or 2 mg/kg body weight flecainide (Fle) for 30 d. Scale bar: 50 μm. B, Quantitation of the number of immunoreactive taste cells per taste bud. Data are expressed as the mean ± SD; n = 60–83 taste buds, each (n = 3 mice). n.s. = no significance.