CONTRIBUTIONS OF A NEGATIVELY CHARGED RESIDUE IN THE HYDROPHOBIC DOMAIN OF THE IRK1 INWARDLY RECTIFYING K-SELECTIVE PERMEATION( CHANNEL TO K+)

Inwardly rectifying K+ channels are highly selective for K+ ions and s how strong interaction with ions in the pore. Both features are import ant for the physiological functions of these channels and pose intrigu ing mechanistic questions of ion permeation. The aspartate residue in the second putative transmembrane segment of the IRK1 inwardly rectify ing K+ channel, previously implicated in inward rectification gating d ue to cytoplasmic Mg2+ and polyamine block, is found in this study to be crucial for the channel's ability to distinguish between K+ and Rb ions. Mutation of this residue also perturbs the interaction between the channel pore and the Sr2+ blocking ion. Our studies suggest that t his aspartate residue contributes to a selectivity filter near the cyt oplasmic end of the pore.