CELL CYCLE-RELATED CHANGES IN THE CONDUCTING PROPERTIES OF R-EAG K+ CHANNELS

Release from arrest in G2 phase of the cell cycle causes profound chan ges in rat ether-h-go-go (r-eag) K+ channels heterologously expressed in Xenopus oocytes. The most evident consequence of the onset of matur ation is the appearance of rectification in the r-eag current. The tri gger for these changes is located downstream of the activation of mito sis-promoting factor (MPF). We demonstrate here that the rectification is due to a voltage-dependent block by intracellular Na+ ions. Manipu lation of the intracellular Na+ concentration indicates that the site of Na+ block is located similar to 45% into the electrical distance of the pore and is only present in oocytes undergoing maturation. Since the currents through excised patches from immature oocytes exhibited a fast rundown, we studied CHO-K1 cells permanently transfected with r- eag. These cells displayed currents with a variable degree of block by Na+ and variable permeability to Cs+. Partial synchronization of the cultures in G0/G1 or M phases of the cell cycle greatly reduced the va riability. The combined data obtained from mammalian cells and oocytes strongly suggest that the permeability properties of r-eag K+ channel s are modulated during cell cycle-related processes.