title: Calcium channels and channelopathies of the central nervous system.
abstract: Several inherited human neurological disorders can be caused by mutations in genes encoding Ca2+ channel subunits. This review deals with known human and mouse calcium channelopathies of the central nervous system (CNS). The human diseases comprise: 1) a recessive retinal disorder, X-linked congenital stationary night blindness, associated with mutations in the CACNA1F gene, encoding alpha(1)1.4 subunits of L-type channels; and 2) a group of rare allelic autosomal dominant human neurological disorders including familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6, all associated with mutations in the CACNA1A gene, encoding alpha(1)2.1 subunits of P/Q-type calcium channels. Mutations at the mouse orthologue of the CACNA1A gene cause a group of recessive neurological disorders, including the tottering, leaner, and rocker phenotypes with ataxia and absence epilepsy, and the rolling Nagoya phenotype with ataxia without seizures. Two other spontaneous mouse mutants with ataxia and absence epilepsy, lethargic and stargazer, have mutations in genes encoding a calcium channel auxiliary beta subunit and a putative calcium channel auxiliary gamma subunit. For each channelopathy, the review describes disease phenotype, channel genotype, and known functional consequences of the pathological mutations; in some cases, it also describes working hypothesis and/or speculations addressing the challenging question of how the alterations in channel function lead to selective cellular dysfunction and disease.
authors.affiliation: Dept of Biomedical Sciences, Univ of Padova, Italy. dani@civ.bio.unipd.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietrobon
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001259:Ataxia / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020013:Calcium Signaling; D002490:Central Nervous System / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000378:metabolism*; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism; D005799:Genes, Dominant; D006429:Hemiplegia / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D017136:Ion Transport; D051379:Mice; D008818:Mice, Neurologic Mutants; D008881:Migraine Disorders / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009755:Night Blindness / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D021122:Protein Subunits
chemical_list: D002118:Calcium; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C105656:CACNA1A protein, human; C113330:CACNA1F protein, human