Combined modulation of the mitochondrial ATP-dependent potassium channel and the permeability transition pore causes prolongation of the biphasic calcium dynamics

Cell Calcium
Yuliya A DahlemThomas F W Horn

Abstract

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 ([Ca(2+)](i)) transients and the mitochondrial membrane potential (psi(m)). For this purpose a model was established exploring the [Ca(2+)](i) transients in N2A cells using continuous application of ATP that causes a biphasic [Ca(2+)](i) response. This response was sensitive to endoplasmatic reticulum (ER) Ca(2+) depletion and a smooth ER Ca(2+)-ATPase (SERCA) antagonist. PTP inhibition by cyclosporine A (CsA) or its non-immunosuppressive derivative NIM811 caused an amplification of the secondary [Ca(2+)](i) peak and induced a hyperpolarization of psi(m). Both the putative mtK-ATP channel inhibitor 5-hydroxydecanoate (5-HD) and the opener diazoxide ameliorated the ATP-induced secondary [Ca(2+)](i) peak. The effect of diazoxide was accompanied by a depolarization of psi(m) whereas 5-HD had no effect on psi(m). When diazoxide and CsA or NIM811 were ...Continue Reading

Citations

Sep 1, 2010·Journal of Ocular Biology, Diseases, and Informatics·Yuan HeJoyce Tombran-Tink
Oct 16, 2007·Doklady. Biochemistry and Biophysics·S M KorotkovN N Ryabchikov
Dec 2, 2008·Biochemical Pharmacology·Anne GieselerPeter Kreutzmann
Jul 10, 2012·Biochimica Et Biophysica Acta·Angelo VianelloMarco Zancani
Feb 6, 2016·International Journal of Oncology·Ingo LangeDana-Lynn Koomoa

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