Transcriptional channelopathies: An emerging class of disorders

Two types of channelopathy are now well recognized: genetic, in which ion c hannels function abnormally or fail to function as a result of mutations, a nd autoimmune, in which antibodies perturb channel function. Recent studies have provided growing evidence for the existence of a third type-transcrip tional channelopathies-which result from changes in the expression of non-m utated channel genes. A well-studied example is peripheral nerve injury, wh ich causes spinal sensory neurons to turn off some active sodium channel ge nes and turn on others that were previously silent, a set of changes that c an result in hyperexcitability of these cells. Recent studies have also sho wn upregulated expression of sensory-neuron-specific sodium channels in Pur kinje cells, indicating that a transcriptional channelopathy might perturb cerebellar function in multiple sclerosis. It is probable that we will soon recognize further disorders that are characterized by dysregulation of cha nnel gene expression in neurons. A better understanding of transcriptional channelopathies might provide us with new opportunities to treat these diso rders.