A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura.

摘要: Migraine with aura is a common, debilitating, recurrent headache disorder associated transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord channel (TRESK, encoded by KCNK18), in pain pathways general anaesthesia. We therefore examined whether TRESK involved migraine screening KCNK18 gene subjects diagnosed migraine. Here we report frameshift mutation, F139WfsX24, which segregates perfectly typical large pedigree. also identified prominent expression migraine-salient areas such as trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes complete loss function mutant subunit suppresses wild-type through dominant-negative effect, thus explaining dominant penetrance allele. These results support pathogenesis further potential therapeutic target.