Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation

Abstract

Author contributionsNE performed tissue isolation, whole mount preparation and imaging/analysis, and ECG recordings. RRM performed intracardiac recordings, ECG recordings, patch clamp electrophysiology, and analysis of echocardiography and provided mentoring support to NE. SH and CS performed RNA isolations and qPCR experiments and analyses. SW performed cardiac myocyte isolation, picrosirius red staining, imaging, and analysis, and qPCR and analysis. AAB performed the RNA isolation for RNA-Seq. CC performed picrosirius red staining and analysis. LJ and WRA contributed to whole mount image analysis. SN mentored and trained NE in whole mount preparation and imaging analysis. NRM and MSR provided mentorship and funding to RRM. LLI contributed to experimental design and interpretation and provided funding. LFLS provided mentoring and training to NE. NE, RRM, LFLS, and LLI cowrote the manuscript. NE and RRM are recognized as co-first authors. NE and RRM performed equal amounts of work and so their authorship is listed in alphabetical order.

Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline‐induced pulmonary hypertension

“…Atrial fibrillation is defined as a supraventricular tachyarrhythmia with uncoordinated atrial electrical activation and consequently ineffective atrial contraction 3 . Inherited 4,5 and acquired 6 heart disease may lead to atrial fibrillation. Importantly, the injury that induces atrial fibrillation may be primary, in the heart tissue, or may be secondary, as is observed in atrial fibrillation due to pulmonary hypertension (PH).…”

Cardiac sodium channel complexes and arrhythmia: structural and functional roles of the β1 and β3 subunits

“…Atrial arrhythmic phenotypes also occur in neonatal Scn1b knockout and adult Scn3b knockout models (Hakim et al., 2010 ; Ramos‐Mondragon et al., 2022 ). The Scn1b knock‐out model shows increased fibrosis, increased action potential duration and pacing‐induced AF.…”

“…Activation and inactivation gating properties were unaffected. Interestingly, these mice also displayed a reduction of the L‐type Ca 2+ current ( I CaL ) (Ramos‐Mondragon et al., 2022 ). These features would together be expected to result in a moderate gain of atrial Na V 1.5 function in parallel with the ventricular LQT3 type phenotype (Lopez‐Santiago et al., 2007 ).…”

Subcellular dynamics and functional activity of the cleaved intracellular domain of the Na+ channel β1 subunit

“…Variants in SCN1B , encoding β1, are associated with developmental and epileptic encephalopathy, early infantile developmental and epileptic encephalopathy, genetic epilepsy with febrile seizures plus, atrial fibrillation and Brugada syndrome ( 31 , 32 , 33 , 34 ). Scn1b null mice display early infantile developmental and epileptic encephalopathy and disrupted neuronal pathfinding and fasciculation, as well as altered cardiac excitability ( 12 , 13 , 35 , 36 ). VGSCs are also aberrantly expressed in cancer cells ( 37 ).…”