Increased Early Sodium Contemporary Provokes Familial Atrial Traumatic Inflammation and Decreases Effectiveness of Sodium Channel Block
Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Atrial fibrillation often develops due to the complication of cardiovascular disease in combination with existing atrial substrates. Familial early-onset AF allows identification of this substrate. Pathogenic manifolds of genes encoding ion channels are associated with familial atrial fibrillation. A point mutation M1875T in the gene, which encodes the -subunit of the cardiac sodium channel Nav1.5, is associated with increased atrial excitability and familial atrial fibrillation. The development of a new mouse model with the Scn5aM1875T mutation allowed us to study this atrial substrate in detail. Methods and Results: Left atrial cardiomyocytes from newly generated Scn5aM1875T + / mice showed a selective increase in early (peak) cardiac sodium current measured by patch clamp. Microelectrode recordings of the intact left atrium showed larger action potential amplitudes and faster peak velocities at upstroke. The line was investigated using optical mapping. When challenged with the sodium channel blocker flecainide, Scn5aM1875T + / left atrium had less conduction velocity reduction than the corresponding wild-type atrium. Electrocardiography and echocardiography, and analysis using cardiac histology, ruled out overt hypertrophy or heart failure in young adults.
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