Figure 2.

Summary of dysfunction along the brain-heart axis in Kcna1^–/– mice. Kcna1^–/– mice exhibit: (1) spontaneous tonic-clonic seizures which manifest as epileptiform electrographic activity in the brain [33]; (2) increased susceptibility to spontaneous ectopic action potential firing in the presence of 4-aminopyridine in myelinated vagus nerve axons [46]; (3) increased susceptibility to intracardiac-pacing induced atrial fibrillation and prolongation of action potential duration in atrial cardiomyocytes [57,58]; (4) increased frequency of atrioventricular (AV) nodal conduction blocks [35]; and (5) bradycardia during seizures [35,39]. In addition, analyses of brain-heart interaction dynamics reveals that Kcna1^–/– mice have significantly decreased brain-heart association, which could be indicative of abnormal uncoupling of brain and heart activity that increases risk of sudden death [47].