Topic: voltage-gated potassium channel

The KCNH2 gene-encoded KV11.1 voltage-gated potassium channel, also known as hERG, is abundantly expressed in the heart and brain, and plays an essential role in stabilizing cardiac and neuronal membrane potentials. Loss-of-function KCNH2 mutations, as well as pharmacological suppressions of human KV11.1 channel function, have been associated with arrhythmia and epilepsy. The majority of disease-related mutations involve aberrant KV11.1 protein folding, resulting in enhanced endoplasmic reticulum (ER)-associated degradation and decreased cell-surface protein level. Despite previous identificat

We recently identified a novel p.Lys376Val variant in KCNA6–encoding the voltage-gated potassium channel Kv1.6–that has been implicated in childhood epilepsy. Here, we aimed to identify the mechanisms by which the variant could contribute to disease.We first synthesized WT and p.Lys376Val KCNA6 and subcloned the cDNA in p.GFP-IRES plasmids. WT, p.Lys376Val and WT + p.Lys376Val (at a 50:50 ratio) were transfected in HEK-293T cells. We characterized the resulting potassium currents using standard voltage clamp techniques. When expressed alone, the KCNA6-p.Lys376Val variant led to a 50% decrease