Artículo
Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
Tubert, Cecilia
; Taravini, Irene Rita Eloisa
; Flores Barrera, Eden; Sanchez, Gonzalo Manuel
; Prost, María Alejandra
; Avale, Maria Elena
; Tseng, Kuei Y.; Rela, Lorena
; Murer, Mario Gustavo
Fecha de publicación:
09/2016
Editorial:
Elsevier
Revista:
Cell Reports
ISSN:
2211-1247
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The mechanism underlying a hypercholinergic state in Parkinson’s disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.
Palabras clave:
Parkinson´S Disease
,
Striatal Cholinergic Interneurons
,
Excitability
,
Kv1.3
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Identificadores
Colecciones
Articulos(IFIBIO HOUSSAY)
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Articulos(INGEBI)
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Citación
Tubert, Cecilia; Taravini, Irene Rita Eloisa; Flores Barrera, Eden; Sanchez, Gonzalo Manuel; Prost, María Alejandra; et al.; Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism; Elsevier; Cell Reports; 16; 10; 9-2016; 2749-2762
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