Publication date: Available online 18 March 2017
Source:Neurobiology of Aging
Author(s): Flavia R. Silva, Artur S. Miranda, Rebeca P.M. Santos, Isabella G. Olmo, Gerald W. Zamponi, Tomas Dobransky, Jader S. Cruz, Luciene B. Vieira, Fabiola M. Ribeiro
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 WT 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 two 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.
http://ift.tt/2nndjyp
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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Σάββατο 18 Μαρτίου 2017
N-type Ca2+ channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington’s disease
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