POTASSIUM CHANNEL BLOCK BY CYTOPLASMIC POLYAMINES AS THE MECHANISM OFINTRINSIC RECTIFICATION

INWARDLY rectifying potassium channels conduct ions more readily in th e inward than the outward direction, an essential property for normal electrical activity(1,2). Although voltage-dependent block by internal magnesium ions may underlie inward rectification in some channels(3-5 ), an intrinsic voltage-dependent closure of the channel plays a contr ibutory, or even exclusive, role in others(4,6-9). Here me report that , rather than being intrinsic to the channel protein, so-called intrin sic rectification of strong inward rectifiers requires soluble factors that are not Mg2+ and can be released from Xenopus oocytes and other cells. Biochemical and biophysical characterization identifies these f actors as polyamines (spermine, spermidine, putrescine and cadaverine) . The results suggest that intrinsic rectification results from voltag e-dependent block of the channel pore by polyamines, not from a voltag e sensor intrinsic to the channel protein(10).