Ion channels and membrane rafts in apoptosis

Ion channels have been demonstrated to be a central element in the induction and the execution of apoptosis. In particular, mitochondrial ion channels, including not only the permeability transition pore but also a mitochondrial, ATP-sensitive (mK(ATP)) channel as well as a mitochondrial calcium-activated potassium channel are involved critically in apoptotic changes in mitochondria. Ion channels in the cell membrane that are altered by induction of apoptosis include potassium, chloride and calcium channels. The Kv1.3 potassium channel belongs to the best-characterized ion channels involved in apoptosis and a genetic model of cells deficient for Kv1.3 has indicated a critical role for Kv1.3, at least in some forms of apoptosis. The mechanisms regulating ion channels during apoptosis are, however, still poorly defined. Recent studies have suggested a function for distinct membrane domains, termed rafts, in the cell membrane for the regulation of ion channels during apoptosis. Small sphingolipid- and cholesterol-enriched membrane domains are modified by many apoptotic stimuli to form large ceramide-enriched membrane platforms. These platforms serve to cluster receptor molecules, to re-organize intracellular signalling molecules including ion channels, to bring ion channels into close contact with their regulators and/or to separate proteins from a specific ion channel. Finally, the lipid composition of the cell membrane might be involved directly in ion channel regulation.