Abstract 16919: Haploinsufficiency of Scn1b Encoding Sodium Channel Beta1 Subunit Alters Cardiac Function

Diastolic dysfunction is typically observed in the elderly population and is reiterated experimentally in aged rodents, together with enhancement of the late Na+ current in cardiomyocytes, a factor that alters intracellular Ca2+ homeostasis and cell mechanics. Based on the findings that Na+ entry is increased in myocytes lacking the Scn1b gene, which encodes for the Na+ channel beta1 subunit, heterozygous mice with inducible Scn1b deletion were employed to establish a putative link between altered Na+ influx in myocytes and defective myocardial relaxation and diastolic dysfunction. Animals were treated with tamoxifen to promote Scn1b loss of function (Scn1b-LOF) and compared to non-treated mice (control, Ctrl). Cardiac function and mechanical properties of myocytes were evaluated in vivo and isolated cell preparations. The QT interval of the ECG was prolonged by 12% in Scn1b-LOF (n=18) with respect to Ctrl mice (n=11) and this repolarization defect was abrogated by administration of mexiletine, a late Na+...