https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Divergent regulation of ryanodine receptor 2 calcium release channels by arrhythmogenic human calmodulin missense mutants https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19035 Sat 24 Mar 2018 08:05:26 AEDT ]]> Inhibition of cardiac Ca²⁺ release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17743 -/- myocytes, the propafenone enantiomers and flecainide significantly reduced arrhythmogenic Ca²⁺ waves at clinically relevant concentrations, whereas Na⁺ channel inhibitors without RyR2 blocking properties did not. In Casq2-/- mice, 5 mg/kg R-propafenone or 20 mg/kg S-propafenone prevented exercise-induced CPVT, whereas procainamide (20 mg/kg) or lidocaine (20 mg/kg) were ineffective (n=5 to 9 mice, P<0.05). QRS duration was not significantly different, indicating a similar degree of Na⁺ channel inhibition. Clinically, propafenone (900 mg/d) prevented ICD shocks in a 22-year-old CPVT patient who had been refractory to maximal standard drug therapy and bilateral stellate ganglionectomy. RyR2 cardiac Ca²⁺ release channel inhibition appears to determine efficacy of class I drugs for the prevention of CPVT in Casq2-/- mice. Propafenone may be an alternative to flecainide for CPVT patients symptomatic on β-blockers.]]> Sat 24 Mar 2018 07:57:39 AEDT ]]>