title: Striatal potassium channel dysfunction in Huntington's disease transgenic mice.
abstract: Huntington's disease (HD) is a neurodegenerative disorder that mainly affects the projection neurons of the striatum and cerebral cortex. Genetic mouse models of HD have shown that neurons susceptible to the mutation exhibit morphological and electrophysiological dysfunctions before and during development of the behavioral phenotype. We used HD transgenic mouse models to examine inwardly and outwardly rectifying K+ conductances, as well as expression of some related K+ channel subunits. Experiments were conducted in slices and dissociated cells from two mouse models, the R6/2 and TgCAG100, at the beginning and after full development of overt behavioral phenotypes. Striatal medium-sized spiny neurons (MSNs) from symptomatic transgenic mice had increased input resistances, depolarized resting membrane potentials, and reductions in both inwardly and outwardly rectifying K+ currents. These changes were more dramatic in the R6/2 model than in the TgCAG100. Parallel immunofluorescence studies detected decreases in the expression of K+ channel subunit proteins, Kir2.1, Kir2.3, and Kv2.1 in MSNs, which contribute to the formation of the channel ionophores for these currents. Attenuation in K+ conductances and channel subunit expression contribute to altered electrophysiological properties of MSNs and may partially account for selective cellular vulnerability in the striatum.
authors.affiliation: Mental Retardation Research Center, NPI Room 58-258, 760 Westwood Plaza, University of California, Los Angeles, CA 90095, USA.
authors.forename: Marjorie A
authors.initials: MA
authors.lastname: Ariano
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Calvert
authors.forename: Jorge
authors.initials: J
authors.lastname: Flores-Hernández
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hernández-Echeagaray
authors.forename: Gloria J
authors.initials: GJ
authors.lastname: Klapstein
authors.forename: Scott H
authors.initials: SH
authors.lastname: Chandler
authors.forename: Neil
authors.initials: N
authors.lastname: Aronin
authors.forename: Marian
authors.initials: M
authors.lastname: DiFiglia
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D002586:Cesium / Q000494:pharmacology; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000502:physiology; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D017072:Neostriatum / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D002586:Cesium; D019789:Tetraethylammonium