Changes in intracellular sodium, chlorine, and potassium concentrations in staurosporine‐induced apoptosis

Abstract

Ion gradients across the plasma membrane, fundamentally K(+), play a pivotal role in the execution phase of apoptosis. However, little is known about other monovalent anions (Cl(-)) or cations (Na(+)) in apoptosis. In addition, the relationship between changes in total ion composition and morphological and biochemical events are poorly understood. We investigated simultaneous changes in sodium (Na), chlorine (Cl), and potassium (K) concentrations in stauroporine-induced apoptosis by quantitative electron probe X-ray microanalysis (EPXMA) in single cells. Apoptotic cells identified unequivocally from the presence of chromatin condensation in backscattered electron images were characterized by an increase in intracellular Na, a decrease in intracellular Cl and K concentrations, and a decrease in K/Na ratio. The ouabain-sensitive Rb-uptake assay demonstrated a net decrease in Na(+)/K(+)-ATPase activity, suggesting that increases in Na and decreases in K and the K/Na ratio in apoptotic cells were related with inhibition of the Na(+)/K(+)-ATPase pump. These changes in diffusible elements were associated with externalization of phosphatidyl serine and oligonucleosomal fragmentation of DNA. This alteration in ion homeostasis and morphological hallmarks of apoptosis occur in cells that have lost their inner mitochondrial transmembrane potential and before the plasma membrane becomes permeable.

Clinical dose of lidocaine destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron

“…, Na ? , and pH can result in apoptosis or necrosis [15][16][17]. For example, dynamic membrane blebbing is caused by the increased contractility of the acto-myosin system following myosin light chain (MLC) phosphorylation.…”

Possible causes of apoptotic volume decrease: an attempt at quantitative review

“…Nevertheless, neurons, like other cells, undergo marked shrinkage during apoptosis (14,18,121). Large experimental errors in Cl Ϫ measurements are unlikely, because ion concentrations have been measured by four different techniques: radioactive (129) or fluorescent ratiometric (50) probes, coulometric titration (98), and X-ray microanalysis (4,6).…”

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

“…Several studies point out that it is not the specific ion per se that is involved in the apoptotic signaling, but rather a decrease in intracellular ionic strength (Arrebola et al, 2006(Arrebola et al, , 2005a(Arrebola et al, , 2005bHughes et al, 1997;Perez et al, 2000). Furthermore, increase in ionic strength has been shown to block the cytochrome c activated caspase-3 pathway (Hampton et al, 1998 (Ye et al, 2008).…”

“…STS is a broad-spectrum protein kinase inhibitor that induces apoptosis (Bertrand et al, 1994;Tamaoki et al, 1986). STS-treatment changes the intracellular ionic composition in several different cell types (Arrebola et al, 2005a(Arrebola et al, , 2005b. In paper III, X. laevis oocytes were also centrifuged to induce apoptosis mechanically.…”