One gene affects multiple organs increasing death risk
Sudden unexpected death in epilepsy (SUDEP) remains the leading cause of epilepsy-related mortality. Despite the historical enigma surrounding its mechanisms, recent findings from the US lab of SMU Biology Professor Edward Glasscock are shedding light on the issue.
In a study published in Brain Communications, Kelsey Paulhus, a post-doctoral researcher in the Glasscock lab and lead author, highlights the significant role of excitatory neurons within the brain’s corticolimbic circuits in epilepsy and SUDEP. This research is the first to demonstrate that circuits lacking the Kv1.1 protein in this subset of neurons promote seizures that can lead to fatal cardiorespiratory failure.
Paulhus said, “For a long time, SUDEP has been suspected to involve a fatal breakdown in communication between the brain, heart, and lungs. In this study, we observed this breakdown in real time using simultaneous recordings of brain, heart, and lung activity in mice lacking Kv1.1 in select brain circuits.”
Glasscock noted the rarity of observing the physiological mechanisms associated with lethal seizures, stating, “Given the unpredictable nature of SUDEP, observing these mechanisms is challenging and has only been accomplished experimentally a handful of times worldwide. This work provides a rare glimpse into the potential sequence of events leading to sudden death in epilepsy.”
The Kv1.1 protein, encoded by the Kcna1 gene, belongs to a family of voltage-gated potassium channels crucial for controlling signals in and between brain and heart cells. Mutations in Kcna1 are a common genetic cause of epilepsy, with more severe mutations leading to epileptic encephalopathy and an increased risk of SUDEP.
Given the unpredictable nature of SUDEP, observing these mechanisms is challenging and has only been accomplished experimentally a handful of times worldwide. This work provides a rare glimpse into the potential sequence of events leading to sudden death in epilepsy.
Professor Edward Glasscock
In another study from the Glasscock lab, published in the Journal of General Physiology, post-doctoral fellow Man Si and colleagues investigated the role of Kv1.1 in cardiac pacemaker cells. They discovered that the absence or blockage of Kv1.1 disrupts normal electrical activity in these cells, resulting in abnormal heart rhythms.
Glasscock emphasised the importance of Kv1.1 in maintaining proper brain and heart function, suggesting that mutations affecting this protein could represent a significant genetic risk factor for SUDEP. These studies underscore Kv1.1 as a critical research target for understanding the complex multi-organ causes of SUDEP.
