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Scn1b plays essential roles in the heart, where it encodes β1-subunits that serve as modifiers of gene expression, cell surface channel activity, and cardiac conductivity. Reduced β1 function is linked to electrical instability in various diseases with cardiac manifestations and increased susceptibility to arrhythmias. Recently, we demonstrated that loss of Scn1b in mice leads to compromised mitochondria energetics and reactive oxygen species (ROS) production. In this study, we examined the link between increased ROS and arrhythmia susceptibility in Scn1b−/− mice. In addition, ROS-scavenging capacity can be overwhelmed during prolonged oxidative stress, increasing arrhythmia susceptibility. Therefore, we isolated whole hearts and cardiomyocytes from Scn1b−/− and Scn1b+/+ mice and subjected them to an oxidative challenge with diamide, a glutathione oxidant. Next, we analyzed gene expression and activity of antioxidant enzymes in Scn1b−/− hearts. Cells isolated from Scn1b−/− hearts died faster and displayed higher rates of ROS accumulation preceding cell death compared with those from Scn1b+/+. Furthermore, Scn1b−/− hearts showed higher arrhythmia scores and spent less time free of arrhythmia. Lastly, we found that protein expression and enzymatic activity of glutathione peroxidase is increased in Scn1b−/− hearts compared with wild type. Our results indicate that Scn1b−/− mice have decreased capability to manage ROS during prolonged oxidative stress. ROS accumulation is elevated and appears to overwhelm ROS scavenging through the glutathione system. This imbalance creates the potential for altered cell energetics that may underlie increased susceptibility to arrhythmias or other adverse cardiac outcomes. NEW & NOTEWORTHY: Using an oxidative challenge, we demonstrated that isolated cells from Scn1b−/− mice are more susceptible to cell death and surges in reactive oxygen species accumulation. At the whole organ level, they were also more susceptible to the formation of cardiac arrhythmias. This may in part be due to changes to the glutathione antioxidant system. [ABSTRACT FROM AUTHOR]

This article discusses a study that investigates the role of the Scn1b gene in cardiac energetics. The researchers focused on mice lacking Scn1b and examined if these mice had compromised mitochondrial energetics. The results showed that the loss of the β1 subunit in the heart led to decreased mitochondrial respiration and increased reverse electron transport. These findings suggest that targeting mitochondrial deficits could be a potential therapeutic approach for reducing the risk of cardiac arrhythmias and cardiovascular disease in individuals with Scn1b mutations. [Extracted from the article]