title: Homeostatic compensation maintains Ca2+ signaling functions in Purkinje neurons in the leaner mutant mouse.
abstract: Several human neurological disorders have been associated with mutations in the gene coding for the alpha1 subunit of the P/Q type voltage-gated calcium channel (alpha1A/Ca(v)2.1). Mutations in this gene also occur in a number of neurologically affected mouse strains, including leaner (tg(la)/tg(la)). Because the P-type calcium current is very prominent in cerebellar Purkinje neurons, these cells from mice with alpha1 subunit mutations make excellent models for the investigation of the functional consequences of native mutations in a voltage-gated calcium channel of mammalian central nervous system. In this review, we describe the impact of altered channel function on cellular calcium homeostasis and signaling. Remarkably, calcium buffering functions of the endoplasmic reticulum and calcium-binding proteins appear to be regulated in order to compensate for altered calcium influx through the mutant channels. Although this compensation may serve to maintain calcium signaling functions, such as calcium-induced calcium release, it remains uncertain whether such compensation alleviates or contributes to the behavioral phenotype.
authors.affiliation: Department of Medical Pharmacology & Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA.
authors.forename: David
authors.initials: D
authors.lastname: Murchison
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Dove
authors.forename: Louise C
authors.initials: LC
authors.lastname: Abbott
authors.forename: William H
authors.initials: WH
authors.lastname: Griffith
mesh_terms: D000818:Animals; D002021:Buffers; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008959:Models, Neurological; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D013851:Thinness / Q000235:genetics
chemical_list: D002021:Buffers; D015220:Calcium Channels