Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy.
Ann Neurol
; 60(5): 586-596, 2006 Nov.
Article
en En
| MEDLINE
| ID: mdl-17044011
ABSTRACT
OBJECTIVE:
We asked whether blockade of voltage-gated K+ channel Kv1.1, whose altered axonal localization during myelin insult and remyelination may disturb nerve conduction, treats experimental autoimmune encephalomyelitis (EAE).METHODS:
Electrophysiological, cell proliferation, cytokine secretion, immunohistochemical, clinical, brain magnetic resonance imaging, and spectroscopy studies assessed the effects of a selective blocker of Kv1.1, BgK-F6A, on neurons and immune cells in vitro and on EAE-induced neurological deficits and brain lesions in Lewis rats.RESULTS:
BgK-F6A increased the frequency of miniature excitatory postsynaptic currents in neurons and did not affect T-cell activation. EAE was characterized by ventriculomegaly, decreased apparent diffusion coefficient, and decreased (phosphocreatine + beta-adenosine triphosphate)/inorganic phosphate ratio. Reduced apparent diffusion coefficient and impaired energy metabolism indicate astrocytic edema. Intracerebroventricularly BgK-F6A-treated rats showed attenuated clinical EAE with unexpectedly reduced ventriculomegaly and preserved apparent diffusion coefficient values and (phosphocreatine + beta-adenosine triphosphate)/inorganic phosphate ratio. Thus, under BgK-F6A treatment, brain damage was dramatically reduced and energy metabolism maintained.INTERPRETATION:
Kv1.1 blockade may target neurons and astrocytes, and modulate neuronal activity and neural cell volume, which may partly account for the attenuation of the neurological deficits. We propose that Kv1.1 blockade has a broad therapeutic potential in neuroinflammatory diseases (multiple sclerosis, stroke, and trauma).
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Venenos de Cnidarios
/
Encefalomielitis Autoinmune Experimental
/
Canales de Potasio de la Superfamilia Shaker
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Ann Neurol
Año:
2006
Tipo del documento:
Article
País de afiliación:
Francia