A STRUCTURAL DETERMINANT OF DIFFERENTIAL SENSITIVITY OF CLONED INWARDRECTIFIER K+ CHANNELS TO INTRACELLULAR SPERMINE

Large subtype-specific differences in the sensitivity of cloned inward -rectifier K+ channels of the IRK1, BIR10 and ROMK1 subtype to being b locked by intracellular spermine (SPM) are described. It is shown, by site-directed mutagenesis, that the four orders of magnitude larger SP M sensitivity of BIR10 channels compared to ROMK1 channels may be expl ained by a difference in a single amino acid in the putative transmemb rane segment TMII. This residue, a negatively charged glutamate in BIR 10, is homologous to the residue in IRK1 and ROMK1 which has previousl y been shown to change gating properties and Mg2+ sensitivity. Differe ntial block by physiological SPM concentrations is suggested as a majo r functional difference between subtypes of inward-rectifer K+ channel s.