Introduction: Mutations in the ryanodine receptor 2 (RyR2) calcium release channel are commonly associated with abnormal diastolic Ca2+ release and catecholaminergic polymorphic ventricular tachycardia (CVPT)1. The RyR2-P2328S mutation, first identified in a Finnish family, has additionally been linked to atrial arrhythmogenicity. A reduced conduction velocity and INa in association with reduced Nav1.5 expression has been demonstrated to contribute to the arrhythmic phenotype in murine RyR2-P2328S (RyR2S/S) atria2. However, whether this reduced Nav1.5 expression is also observed in the RyR2S/S ventricle has not been established. This study assessed whether a reduction in Nav1.5 is also observed in the ventricle, particularly within the membrane fraction, and correlated this with measures of arrhythmogenicity, action potential restitution and conduction. Methods: WT and RyR2S/S mice were killed by cervical dislocation (Schedule 1, ASPA 1986), their hearts rapidly removed, snap frozen in liquid N2, homogenised in resuspension and lysis buffers in the presence of protease inhibitors, separated by centrifugation to obtain whole tissue and membrane fractions, and run against suitable markers. Programmed electrical stimulation (PES), standard S1S2 and dynamic restitution protocols, applied to Langendorff-perfused hearts, provided measures of arrhythmic incidence, action potential duration at 90% recovery (APD90) and conduction latency. Data are means ± SEM or % expression relative to WT and were compared by unpaired students t-test. Results: Nav1.5 expression was significantly reduced in the ventricle of RyR2S/S hearts compared to WT by 20% within the whole tissue fraction and more notably by 40 % within the membrane fraction (Figure 1.). RyR2S/S hearts were more arrhythmic than WT hearts as previously shown3, ventricular effective refractory period was similar between RyR2S/S (33.50 ± 4.55 ms) and WT (39.38 ± 4.16) hearts, and the maximum slope of the APD90 restitution curve was increased in the RyR2S/S. While conduction latency was similar between RyR2S/S (24.36 ± 2.08 ms) and WT hearts (19.06 ± 1.12 ms, P > 0.05) at 8 Hz pacing, RyR2S/S hearts had a much higher conduction latency compared to WT at the fastest pacing frequencies attained just prior to refractoriness or arrhythmia (36.44 ± 1.76 and 26.52 ±1.19 ms respectively, P < 0.05). Discussion: Reduced Nav1.5 expression in RyR2S/S ventricles contributes to the slowed conduction, abnormal repolarisation and increased arrhythmogenicity. This is in accordance with previous findings within atrial myocardium4.