title: CaV2.1 channelopathies.
abstract: Mutations in the CACNA1A gene that encodes the pore-forming alpha1 subunit of human voltage-gated CaV2.1 (P/Q-type) Ca2+ channels cause several autosomal-dominant neurologic disorders, including familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2, and spinocerebellar ataxia type 6 (SCA6). For each channelopathy, the review describes the disease phenotype as well as the functional consequences of the disease-causing mutations on recombinant human CaV2.1 channels and, in the case of FHM1 and SCA6, on neuronal CaV2.1 channels expressed at the endogenous physiological level in knockin mouse models. The effects of FHM1 mutations on cortical spreading depression, the phenomenon underlying migraine aura, and on cortical excitatory and inhibitory synaptic transmission in FHM1 knockin mice are also described, and their implications for the disease mechanism discussed. Moreover, the review describes different ataxic spontaneous cacna1a mouse mutants and the important insights into the cerebellar mechanisms underlying motor dysfunction caused by mutant CaV2.1 channels that were obtained from their functional characterization.
authors.affiliation: Department of Biomedical Sciences, University of Padova, 35121, Padua, Italy. daniela.pietrobon@unipd.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietrobon
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics; D020864:Calcium Channels, N-Type / Q000235:genetics* / Q000502:physiology; D053447:Channelopathies / Q000235:genetics*; D013181:Cortical Spreading Depression / Q000235:genetics; D055879:Gene Knock-In Techniques; D006801:Humans; D051379:Mice; D020325:Migraine with Aura / Q000235:genetics; D023421:Models, Animal; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D011994:Recombinant Proteins; C105656:CACNA1A protein, human