کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2166427 1091854 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The α2δ subunit augments functional expression and modifies the pharmacology of CaV1.3 L-type channels
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
The α2δ subunit augments functional expression and modifies the pharmacology of CaV1.3 L-type channels
چکیده انگلیسی

The auxiliary CaVα2δ-1 subunit is an important component of voltage-gated Ca2+ (CaV) channel complexes in many tissues and of great interest as a drug target. Nevertheless, its exact role in specific cell functions is still unknown. This is particularly important in the case of the neuronal L-type CaV channels where these proteins play a key role in the secretion of neurotransmitters and hormones, gene expression, and the activation of other ion channels. Therefore, using a combined approach of patch-clamp recordings and molecular biology, we studied the role of the CaVα2δ-1 subunit on the functional expression and the pharmacology of recombinant L-type CaV1.3 channels in HEK-293 cells. Co-expression of CaVα2δ-1 significantly increased macroscopic currents and conferred the CaV1.3α1/CaVβ3 channels sensitivity to the antiepileptic/analgesic drugs gabapentin and AdGABA. In contrast, CaVα2δ-1 subunits harboring point mutations in N-glycosylation consensus sequences or the proteolytic site as well as in conserved cysteines in the transmembrane δ domain of the protein, reduced functionality in terms of enhancement of CaV1.3α1/CaVβ3 currents. In addition, co-expression of the δ domain drastically inhibited macroscopic currents through recombinant CaV1.3 channels possibly by affecting channel synthesis. Together these results provide several lines of evidence that the CaVα2δ-1 auxiliary subunit may interact with CaV1.3 channels and regulate their functional expression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 46, Issue 4, October 2009, Pages 282–292
نویسندگان
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