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Our data show that KCOs under study not only activate mitoBKCa channels from brain tissue, but also induce cell death when used in cellular models. The cytotoxic effect of the channel opener was partially reversed by a calpain inhibitor. CGS7184 treatment resulted in an increase of cytoplasmic Ca2+ concentration that likely involved efflux from internal calcium stores and the activation of calpains (calcium-dependent proteases. CGS7184 toxicity was not abolished by BKCa channel inhibitors, suggesting that the observed effects were independent of a BKCa-type channel activity. By contrast, we did not observe cell death when NS1619 or NS004 was applied. However, experiments on intact neuronal HT22 cells revealed that both CGS7181 and CGS7184 induced HT22 cell death in a concentration- and time-dependent manner.

Moreover, when applied to the rat brain homogenate or isolated rat brain mitochondria, CGS7184 increased the oxygen consumption rate, and can thus be considered a potentially cytoprotective agent. We showed that CGS7184 activated the mitochondrial BKCa (mitoBKCa channel in single-channel recordings performed on astrocytoma mitoplasts. For the purpose of this research, we used a rat brain, the mouse hippocampal HT22 cells, and the human astrocytoma U-87 MG cell line. In the present study, we investigated the effects of BKCa channel openers CGS7181, CGS7184, NS1619, and NS004 in neuronal cells.

Recently, in several reports, a number of data has been described as off-target actions for KCOs. Mitochondrial BK Channel Openers CGS7181 and CGS7184 Exhibit Cytotoxic Propertiesĭirectory of Open Access Journals (Sweden)įull Text Available Potassium channel openers (KCOs have been shown to play a role in cytoprotection through the activation of mitochondrial potassium channels. Observatorio Astroonomico Nacional Yebes.

Fundamental-station Wettzell 20m Radiotelescope. JARE Syowa Station 11-m Antenna, Antarctica. 10 Years of Geodetic Experiments at the Simeiz VLBI Station.

The IVS network station Onsala space Observatory. German Antarctic receiving Station (GARS) O'higgins. Hbart, Mt Pleasant, station report for 2004. Hartebeesthoek Radio Astronomy Observatory (HartRAO). Goddard Geophysical and Astronomical observatory. (Editor)Ĭontents include the following: Combination Studies using the Cont02 Campaign. International VLBI Service for Geodesy and Astrometry 2004 Annual Reportīehrend, Dirk (Editor) Baver, Karen D.

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