title: Neuronal P/Q-type calcium channel dysfunction in inherited disorders of the CNS.
abstract: The past two decades have witnessed the emergence of a new and expanding field of neurological diseases--the genetic ion channelopathies. These disorders arise from mutations in genes that encode ion channel subunits, and manifest as paroxysmal attacks involving the brain or spinal cord, and/or muscle. The voltage-gated P/Q-type calcium channel (P/Q channel) is highly expressed in the cerebellum, hippocampus and cortex of the mammalian brain. The P/Q channel has a fundamental role in mediating fast synaptic transmission at central and peripheral nerve terminals. Autosomal dominant mutations in the CACNA1A gene, which encodes voltage-gated P/Q-type calcium channel subunit α(1) (the principal pore-forming subunit of the P/Q channel) are associated with episodic and progressive forms of cerebellar ataxia, familial hemiplegic migraine, vertigo and epilepsy. This Review considers, from both a clinical and genetic perspective, the various neurological phenotypes arising from inherited P/Q channel dysfunction, with a focus on recent advances in the understanding of the pathogenetic mechanisms underlying these disorders.
authors.affiliation: Medical Research Council Center for Neuromuscular Diseases, Box 102, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Rajakulendran
authors.forename: Diego
authors.initials: D
authors.lastname: Kaski
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000145:classification / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000502:physiology*
chemical_list: D020864:Calcium Channels, N-Type