IKCa1 activity is required for cell shrinkage, phosphatidylserine translocation and death in T lymphocyte apoptosis.
Apoptotic cell volume decrease (AVD) and exposure of phosphatidylserine (PtdSer) at the cell surface are early events in apoptosis. However, the ion channels responsible for AVD, and their relationship to PtdSer translocation and cell death are poorly understood. Real-time analysis of calcium-induced apoptosis in lymphocytes and thymocytes showed that AVD occurs rapidly, and precedes PtdSer translocation. Blockers of the K(+) channel IKCa1 completely inhibited AVD. Blockade of IKCa1, and hence AVD, also completely prevented PtdSer translocation and cell death. Thus, IKCa1-mediated AVD is the earliest-defined essential step in calcium-induced apoptosis, required for both PtdSer translocation and cell death.
Elliott
James I
JI
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Rd, London W12 0NN, UK. james.elliott@csc.mrc.ac.uk
Higgins
Christopher F
CF
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001693:Biological Transport, Active; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D000001:Calcimycin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000502:physiology; D051379:Mice; D010718:Phosphatidylserines / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496925:Kcnn4 protein, mouse; D010718:Phosphatidylserines; D015221:Potassium Channels; D000001:Calcimycin; D002118:Calcium