Potassium channels Kv1.3 and Kv1.5 are expressed on blood-derived dendritic cells in the central nervous system.
Ann Neurol
; 60(1): 118-27, 2006 Jul.
Article
em En
| MEDLINE
| ID: mdl-16729292
ABSTRACT
OBJECTIVE:
Potassium (K(+)) channels on immune cells have gained attention recently as promising targets of therapy for immune-mediated neurological diseases such as multiple sclerosis (MS). We examined K(+) channels on dendritic cells (DCs), which infiltrate the brain in MS and may impact disease course.METHODS:
We identified K(+) channels on blood-derived DCs by whole-cell patch-clamp analysis, confirmed by immunofluorescent staining. We also stained K(+) channels in brain sections from MS patients and control subjects. To test functionality, we blocked K(v)1.3 and K(v)1.5 in stimulated DCs with pharmacological blockers or with an inducible dominant-negative K(v)1.x adenovirus construct and analyzed changes in costimulatory molecule upregulation.RESULTS:
Electrophysiological analysis of DCs showed an inward-rectifying K(+) current early after stimulation, replaced by a mix of voltage-gated K(v)1.3- and K(v)1.5-like channels at later stages of maturation. K(v)1.3 and K(v)1.5 were also highly expressed on DCs infiltrating MS brain tissue. Of note, we found that CD83, CD80, CD86, CD40, and interleukin-12 upregulation were significantly impaired on K(v)1.3 and K(v)1.5 blockade.INTERPRETATION:
These data support a functional role of K(v)1.5 and K(v)1.3 on activated human DCs and further define the mechanisms by which K(+) channel blockade may act to suppress immune-mediated neurological diseases.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Encéfalo
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Doenças do Sistema Nervoso Central
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Canal de Potássio Kv1.5
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Canal de Potássio Kv1.3
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos