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

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 intracel

SUBMITTER: Benitez-Rangel E 

PROVIDER: S-EPMC3077289 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature