کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10926470 1091852 2009 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regulation of voltage-gated Ca2+ channels by lipids
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Regulation of voltage-gated Ca2+ channels by lipids
چکیده انگلیسی
Great skepticism has surrounded the question of whether modulation of voltage-gated Ca2+ channels (VGCCs) by the polyunsaturated free fatty acid arachidonic acid (AA) has any physiological basis. Here we synthesize findings from studies of both native and recombinant channels where micromolar concentrations of AA consistently inhibit both native and recombinant activity by stabilizing VGCCs in one or more closed states. Structural requirements for these inhibitory actions include a chain length of at least 18 carbons and multiple double bonds located near the fatty acid's carboxy terminus. Acting at a second site, AA increases the rate of VGCC activation kinetics, and in CaV2.2 channels, increases current amplitude. We present evidence that phosphatidylinositol 4,5-bisphosphate (PIP2), a palmitoylated accessory subunit (β2a) of VGCCs and AA appear to have overlapping sites of action giving rise to complex channel behavior. Their actions converge in a physiologically relevant manner during muscarinic modulation of VGCCs. We speculate that M1 muscarinic receptors may stimulate multiple lipases to break down the PIP2 associated with VGCCs and leave PIP2's freed fatty acid tails bound to the channels to confer modulation. This unexpectedly simple scheme gives rise to unanticipated predictions and redirects thinking about lipid regulation of VGCCs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 45, Issue 6, June 2009, Pages 589-601
نویسندگان
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