Neurological channelopathies: diagnosis and therapy in the new millennium

Rapid progress in the complementary fields of molecular genetics and cellul ar electrophysiology has led to a better understanding of many disorders wh ich are caused by ion channel dysfunction. These channelopathies may manife st in a multitude of ways depending on the tissue specificity of the channe l that is affected. Several important general medical conditions are now kn own to be channelopathies but the neurological members of this family are a mongst the best characterized. Over recent years, ion channel dysfunction i n skeletal muscle in particular has emerged as a paradigm for understanding neurological ion channel disorders. This review concentrates mainly on the diseases caused by dysfunction of the voltage-gated ion channels. We initi ally focus on the skeletal muscle channelopathies (the periodic paralyses, malignant hyperthermia, paramyotonia congenita and myotonia congenita). The central nervous system channelopathies are then explored, with particular reference to the advances which have implications for understanding the mec hanisms of common neurological disorders such as epilepsy and migraine. Loo king towards the new millennium, DNA-based diagnosis will become a realisti c proposition for most neurological channelopathies. Furthermore, it seems likely that new therapies will be designed based on genotype and mode of io n channel dysfunction.