The role of ionic K+ in the regulation of apoptosis

Cell shrinkage is a major characteristic of apoptotic cell death and is associated with a decrease in intracellular K+ concentration. Intracellular K+ ions have an important role in setting and modulating the plasma membrane potential and can profoundly affect the activity of a number of cellular enzymes.;Following initial investigations into the role of K+ in cell survival and apoptosis in primary cultures of cerebellar granule neurons, flux of cellular K+ following induction of apoptosis by death receptor ligation or chemical stress was assessed in Jurkat T cells loaded with the K+ ion surrogate 86Rb+. A time-dependent efflux of intracellular K+ was demonstrated that accompanies cell shrinkage, reduction of mitochondrial transmembrane potential (m) and phosphatidylserine (PS) externalisation. An apparent increase in mitochondrial K+ concentration following treatment of cells with anti-CD95 antibody was also demonstrated. Induction of CD95- or chemical-mediated apoptosis results in depolarisation of the plasma membrane that accompanies PS externalisation and reduction of m. Both depolarisation of the plasma membrane and efflux of intracellular K+ are dependent upon caspase activation in CD95- but not chemical-mediated apoptosis. Consistent with the hypothesis that efflux of intracellular K+ is required for the progression of apoptosis, formation of the caspase-activating ~700 kDa Apaf-1-containing apoptosome complex is inhibited in vitro by 50mM K+.;The data imply that K+ plays an important role in the regulation and progression of apoptosis by influencing transmembrane voltage or ion-sensitive enzymatic processes.