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N-type Ca2+ channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington's disease
- Source :
- Neurobiology of Aging. 55:1-10
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein. In addition to facilitating neurodegeneration, mutant htt is implicated in HD-related alterations of neurotransmission. Previous data showed that htt can modulate N-type voltage-gated Ca2+ channels (Cav2.2), which are essential for presynaptic neurotransmitter release. Thus, to elucidate the mechanism underlying mutant htt-mediated alterations in neurotransmission, we investigated how Cav2.2 is affected by full-length mutant htt expression in a mouse model of HD (BACHD). Our data indicate that young BACHD mice exhibit increased striatal glutamate release, which is reduced to wild type levels following Cav2.2 block. Cav2.2 Ca2+ current-density and plasma membrane expression are increased in BACHD mice, which could account for increased glutamate release. Moreover, mutant htt affects the interaction between Cav2.2 and 2 major channel regulators, namely syntaxin 1A and Gβγ protein. Notably, 12-month old BACHD mice exhibit decreased Cav2.2 cell surface expression and glutamate release, suggesting that Cav2.2 alterations vary according to disease stage.
- Subjects :
- 0301 basic medicine
congenital, hereditary, and neonatal diseases and abnormalities
Aging
Huntingtin
Neurotransmission
Biology
03 medical and health sciences
0302 clinical medicine
Huntington's disease
mental disorders
medicine
Huntingtin Protein
Syntaxin
General Neuroscience
Neurodegeneration
Glutamate receptor
Wild type
medicine.disease
Cell biology
030104 developmental biology
nervous system
Biochemistry
Neurology (clinical)
Geriatrics and Gerontology
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 01974580
- Volume :
- 55
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Aging
- Accession number :
- edsair.doi...........22867a67d3e2565e2202da16d40970fb