Skip to main content
. 2014 Dec 23;106(1):143–152. doi: 10.1093/cvr/cvu262

Figure 6.

Figure 6

Effect of neuronal Na+ channel blockade on CPVT. (A) Representative ECG recordings of R33Q mutant mice before (top) and after (bottom) injection (i.p.) of epinephrine (Epi, 1.5 mg/kg) and caffeine (Caff, 120 mg/kg). As illustrated in the ECG trace, Epi + Caff challenge resulted in numerous repetitive ventricular extrasystoles (arrows), bigeminy, and the induction of ventricular tachycardia (VT). (B) ECG of R33Q mice after administration of Ril (10 mg/kg), targeting plasma concentrations comparable to those achieved in experiments conducted in isolated cardiomyocytes,34 before (top) and after (bottom) Epi + Caff challenge. (C) ECG of SN-6 (40 mg/kg) treated mice 10 min before (top) and after (bottom) Epi + Caff challenge. (D) Arrhythmia and (E) ventricular tachycardia (VT) incidence (%) in R33Q mice exposed to Epi + Caff during various interventions (n = 6–11 mice, *P < 0.05). (F) Na+/Ca2+ signalling: colocalization to the same discrete subcellular region allows crosstalk between neuronal Na+ channels (nNav) and leaky Ca2+ release channels (RyR2) through the NCX resulting in aberrant DCR that underlie ventricular extrasystoles, which in turn trigger VT.