Fig. 6.

Scn8a^N1768D/+ mice display characteristics of increased parasympathetic activity and cardiac arrhythmias in vivo. (A) Anesthetized Scn8a^N1768D/+ mice have significantly decreased heart rates (HR, in beats per minute, BPM) compared with WT as assessed by surface ECG (P = 0.03). Administration of 2 mg/kg i.p. NE eliminates this difference (P = 0.39). (B) Denervated ex vivo heart preparations show no differences in heart rate between groups (P = 0.45). (C) Representative surface ECG recording of arrhythmogenic events recorded in two anesthetized Scn8a^N1768D/+ mice after injection of 2 mg/kg i.p. NE and 120 mg/kg i.p. caffeine. Episodes of ventricular tachycardia and premature ventricular beats are circled in the traces. Scn8a^+/+ (WT): n = 6; and Scn8a^N1768D/+ (D/+): n = 5 for in vivo studies. WT: n = 6; and D/+: n = 7 for ex vivo studies. *P < 0.05 vs. WT.