کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2166799 1091887 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Combined modulation of the mitochondrial ATP-dependent potassium channel and the permeability transition pore causes prolongation of the biphasic calcium dynamics
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Combined modulation of the mitochondrial ATP-dependent potassium channel and the permeability transition pore causes prolongation of the biphasic calcium dynamics
چکیده انگلیسی

The permeability transition pore (PTP) and the ATP-dependent potassium (mtK-ATP) channel of mitochondria are known to play key roles in mitochondrially mediated apoptosis. We investigated how modulation of the permeability transition pore (PTP) and the ATP-dependent potassium (mtK-ATP) channel, either as single elements or in combination, affects the proapoptotic intracellular calcium ([Ca2+]i) transients and the mitochondrial membrane potential (ψm). For this purpose a model was established exploring the [Ca2+]i transients in N2A cells using continuous application of ATP that causes a biphasic [Ca2+]i response. This response was sensitive to endoplasmatic reticulum (ER) Ca2+ depletion and a smooth ER Ca2+-ATPase (SERCA) antagonist. PTP inhibition by cyclosporine A (CsA) or its non-immunosuppressive derivative NIM811 caused an amplification of the secondary [Ca2+]i peak and induced a hyperpolarization of ψm. Both the putative mtK-ATP channel inhibitor 5-hydroxydecanoate (5-HD) and the opener diazoxide ameliorated the ATP-induced secondary [Ca2+]i peak. The effect of diazoxide was accompanied by a depolarization of ψm whereas 5-HD had no effect on ψm. When diazoxide and CsA or NIM811 were applied together the secondary [Ca2+]i rise did not return to baseline and a not significant hyperpolarization of ψm was observed. So, simultaneous inhibition of PTP and activation of the mtK-ATP channel prevents the increased slope of the secondary [Ca2+]i peak induced by CsA (or NIM811) and also the depolarization after diazoxide application. Hence, we propose that modulation of one of these channels leads to functional changes of the other channel by means of Δ[Ca2+]i and Δψm.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 39, Issue 5, May 2006, Pages 387–400
نویسندگان
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