| First Author | Silva FR | Year | 2017 |
| Journal | Neurobiol Aging | Volume | 55 |
| Pages | 1-10 | PubMed ID | 28391067 |
| Mgi Jnum | J:244025 | Mgi Id | MGI:5912804 |
| Doi | 10.1016/j.neurobiolaging.2017.03.015 | Citation | Silva FR, et al. (2017) N-type Ca2+ channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington's disease. Neurobiol Aging 55:1-10 |
| abstractText | 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 Gbetagamma 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. |
