NDLI: Ion channel inhibitors block caspase activation by mechanisms other than restoring intracellular potassium concentration

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Benítez-Rangel, E. García, L. Namorado, M. C. Reyes, J. L. Guerrero-Hernández, A.
Description	Author Affiliation: Benítez-Rangel E ( Department of Biochemistry, CINVESTAV-IPN, DF, México.)
Abstract	Ion fluxes at the plasma membrane have an important role in early stages of apoptosis. Accordingly, plasma membrane depolarization and gain of Na(+) and loss of K(+) are initial events in apoptosis. We have studied the effect of staurosporine (STS), a well-established apoptosis inducer, on the membrane potential of HeLa cells to determine the nature of STS-activated ion conductances and their role in the activation of different caspases. We observed that STS can activate tetraethylammonium (TEA(+)) and 4-aminopyridine-sensitive K(+) channels and flufenamic-sensitive cation channels as an early response. The combination of these ion channel inhibitors significantly reduced cytochrome c (cyt c) release and activation of caspase-9, -3 and -8. STS also induced a large reduction in the intracellular [K(+)] that was not blocked by the ion channel inhibitors. Our data suggest that reduction in the [K(+)](i) is necessary but not sufficient and that ion channel inhibitors block activation of caspase-3 by two different mechanisms: the inhibitors of K(+) channels by reducing cyt c release while flufenamic acid by a different, unrelated mechanism that does not involve cation channels at the plasma membrane. Our data also imply that these ion channels activated by STS are not responsible for the reduction in the [K(+)](i) associated with apoptosis.
File Format	HTM / HTML
e-ISSN	20414889
DOI	10.1038/cddis.2010.93
Journal	Cell Death and Disease
Volume Number	2
Language	English
Publisher	Nature Publishing Group
Publisher Date	2011-01-13
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Research Support, Non-u.s. Gov't Enzyme Inhibitors Ion Channels Staurosporine Pharmacology Metabolism Intracellular Space Drug Effects Caspase Inhibitors Antagonists & Inhibitors Discipline Cell Biology Biological Transport Caspases Enzyme Activation Potassium Hela Cells Apoptosis
Content Type	Text
Resource Type	Article

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