title: Localization and behaviors in null mice suggest that ASIC1 and ASIC2 modulate responses to aversive stimuli.
abstract: Acid-sensing ion channels (ASICs) generate H(+) -gated Na(+) currents that contribute to neuronal function and animal behavior. Like ASIC1, ASIC2 subunits are expressed in the brain and multimerize with ASIC1 to influence acid-evoked currents and facilitate ASIC1 localization to dendritic spines. To better understand how ASIC2 contributes to brain function, we localized the protein and tested the behavioral consequences of ASIC2 gene disruption. For comparison, we also localized ASIC1 and studied ASIC1(-/-) mice. ASIC2 was prominently expressed in areas of high synaptic density, and with a few exceptions, ASIC1 and ASIC2 localization exhibited substantial overlap. Loss of ASIC1 or ASIC2 decreased freezing behavior in contextual and auditory cue fear conditioning assays, in response to predator odor and in response to CO2 inhalation. In addition, loss of ASIC1 or ASIC2 increased activity in a forced swim assay. These data suggest that ASIC2, like ASIC1, plays a key role in determining the defensive response to aversive stimuli. They also raise the question of whether gene variations in both ASIC1 and ASIC2 might affect fear and panic in humans.
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Price
authors.forename: H
authors.initials: H
authors.lastname: Gong
authors.forename: M G
authors.initials: MG
authors.lastname: Parsons
authors.forename: J R
authors.initials: JR
authors.lastname: Kundert
authors.forename: L R
authors.initials: LR
authors.lastname: Reznikov
authors.forename: L
authors.initials: L
authors.lastname: Bernardinelli
authors.forename: K
authors.initials: K
authors.lastname: Chaloner
authors.forename: G F
authors.initials: GF
authors.lastname: Buchanan
authors.forename: J A
authors.initials: JA
authors.lastname: Wemmie
authors.forename: G B
authors.initials: GB
authors.lastname: Richerson
authors.forename: M D
authors.initials: MD
authors.lastname: Cassell
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D003214:Conditioning, Classical; D003463:Cues; D005239:Fear; D046352:Freezing Reaction, Cataleptic; D017353:Gene Deletion; D008124:Locomotion; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D057907:Post-Synaptic Density / Q000378:metabolism
chemical_list: C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels
keywords: ASIC1; ASIC2; Acid-sensing ion channel; brain; carbon dioxide; fear conditioning; immunocytochemistry