Neurological channelopathies: diagnosis and therapy in the new millennium

Rapid progress in the complementary fields of molecular genetics and cellular electrophysiology has led to a better understanding of many disorders which are caused by ion channel dysfunction. These channelopathies may manifest in a multitude of ways depending on the tissue specificity of the channel that is affected. Several important general medical conditions are now known to be channelopathies but the neurological members of this family are amongst the best characterized. Over recent years, ion channel dysfunction in 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 initially 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 mechanisms of common neurological disorders such as epilepsy and migraine. Looking towards the new millennium, DNA-based diagnosis will become a realistic proposition for most neurological channelopathies. Furthermore, it seems likely that new therapies will be designed based on genotype and mode of ion channel dysfunction.