Erythrocyte ion channels in regulation of apoptosis

Advances in Experimental Medicine and Biology
Florian LangStephan M Huber

Abstract

Erythrocytes lack mitochondria and nuclei, key organelles in the regulation of apoptosis. Until recently, erythrocytes were thus not considered subject to this type of cell death. However, exposure of erythrocytes to the Ca2+ ionophore ionomycin was shown to induce cell shrinkage, cell membrane blebbing and breakdown of phosphatidylserine asymmetry with subsequent phosphatidylserine exposure at the cell surface, all typical features of apoptosis. Further studies revealed the participation of ion channels in the regulation of erythrocyte "apoptosis." Osmotic shock, oxidative stress and energy depletion all activate a Ca2(+)-permeable non-selective cation channel in the erythrocyte cell membrane. The subsequent increase of Ca2+ concentration stimulates a scramblase leading to breakdown of cell membrane phosphatidylserine asymmetry and activates Ca2+ sensitive K+ (Gardos) channels leading to KCl loss and (further) cell shrinkage. Phosphatidylserine exposure and cell shrinkage are blunted in the nominal absence of extracellular Ca2+, in the presence of the cation channel inhibitors amiloride or ethylisopropylamiloride, at increased extracellular K+ or in the presence of the Gardos channel inhibitors clotrimazole or charybdotoxin. T...Continue Reading

Citations

Sep 25, 2015·Cell Biochemistry and Function·Maria Pagano, Caterina Faggio
Jul 31, 2013·Inflammation·Arif Burak CekicCengiz Erçin
Oct 16, 2012·Pflügers Archiv : European journal of physiology·J Marc SimardVolodymyr Gerzanich
Mar 5, 2014·Human Reproduction Update·Ye Chun RuanHsiao Chang Chan
Jul 8, 2015·Blood·Raphael Rapetti-MaussCatherine Badens
Nov 26, 2009·Journal of Proteomics·Niels LionJean-Daniel Tissot
Feb 12, 2010·Experimental Hematology·Marcel H A M FensRaymond M Schiffelers

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