THE S4-S5 LOOP CONTRIBUTES TO THE ION-SELECTIVE PORE OF POTASSIUM CHANNELS

Mutagenesis experiments on voltage-gated K+ channels have suggested th at the ion-selective pore is comprised mostly of H5 segments. To see w hether regions outside of the H5 segment might also contribute to the pore structure, we have studied the effect of single amino acid substi tutions in the segment that connects the S4 and S5 putative transmembr ane segments (S4-S5 loop) on various permeation properties of Shaker K + channels. Mutations in the S4-S5 loop alter the Rb+ selectivity, the single-channel K+ and Rb+ conductances, and the sensitivity to open c hannel block produced by intracellular tetraethylammonium ion, Ba2+, a nd Mg2+. The block of Shaker K+ channels by intracellular Mg2+ is surp rising, but is reminiscent of the internal Mg2+ blockade of inward rec tifier K+ channels. The results suggest that the S4-S5 loop constitute s part of the ion-selective pore. Thus, the S4-S5 loop and the H5 segm ent are likely to contribute to the long pore characteristic of voltag e-gated K+ channels.