Format

Send to

Choose Destination
See comment in PubMed Commons below
Prog Neurobiol. 2003 Jul;70(4):363-86.

Regulation and critical role of potassium homeostasis in apoptosis.

Author information

  • 1Department of Pharmaceutical Sciences, School of Pharmacy, Medical University of South Carolina, 280 Calhoun Street, PO Box 250140, Charleston, SC 29425, USA. yusp@musc.edu

Abstract

Programmed cell death or apoptosis is broadly responsible for the normal homeostatic removal of cells and has been increasingly implicated in mediating pathological cell loss in many disease states. As the molecular mechanisms of apoptosis have been extensively investigated a critical role for ionic homeostasis in apoptosis has been recently endorsed. In contrast to the ionic mechanism of necrosis that involves Ca(2+) influx and intracellular Ca(2+) accumulation, compelling evidence now indicates that excessive K(+) efflux and intracellular K(+) depletion are key early steps in apoptosis. Physiological concentration of intracellular K(+) acts as a repressor of apoptotic effectors. A huge loss of cellular K(+), likely a common event in apoptosis of many cell types, may serve as a disaster signal allowing the execution of the suicide program by activating key events in the apoptotic cascade including caspase cleavage, cytochrome c release, and endonuclease activation. The pro-apoptotic disruption of K(+) homeostasis can be mediated by over-activated K(+) channels or ionotropic glutamate receptor channels, and most likely, accompanied by reduced K(+) uptake due to dysfunction of Na(+), K(+)-ATPase. Recent studies indicate that, in addition to the K(+) channels in the plasma membrane, mitochondrial K(+) channels and K(+) homeostasis also play important roles in apoptosis. Investigations on the K(+) regulation of apoptosis have provided a more comprehensive understanding of the apoptotic mechanism and may afford novel therapeutic strategies for apoptosis-related diseases.

PMID:
12963093
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk