Plasma membrane potential in thymocyte apoptosis

Apoptosis is accompanied by major changes in ion compartmentalization and t ransmembrane potentials. Thymocyte apoptosis is characterized by an early d issipation of the mitochondrial transmembrane potential, with transient mit ochondrial swelling and a subsequent loss of plasma membrane potential (Del ta Psi(p)) related to the loss of cytosolic K+, cellular shrinkage, and DNA fragmentation. Thus, a gross perturbation of Delta Psi(p) occurs at the po stmitochondrial stage of apoptosis, Unexpectedly, rye found that blockade o f plasma membrane K+ channels by tetrapentylammonium (TPA), which leads to a Delta Psi(p) collapse, can prevent the thymocyte apoptosis induced by exp osure to the glucocorticoid receptor agonist dexamethasone, the topoisomera se inhibitor etoposide, gamma-irradiation, or ceramide, The TPA-mediated pr otective effect extends to all features of apoptosis, including dissipation of the mitochondrial transmembrane potential, loss of cytosolic K+, phosph atidylserine exposure on the cell surface, chromatin condensation, as well as caspase and endonuclease activation, In strict contrast, TPA is an ineff ective inhibitor when cell death is induced by the potassium ionophore vali nomycin, the specific mitochondrial :benzodiazepine ligand PK11195, or by p rimary caspase activation by Fas/CD95 cross-linking. These results underlin e the importance of K+ channels for the regulation of some but not all path ways leading to thymocyte apoptosis.