Gating charge differences between two voltage-gated K+ channels are due to the specific charge content of their respective S4 regions.

Voltage-gated ion channels that differ in their primary amino acid sequence in the putative voltage sensor, the S4 region, show distinct voltage-sensing characteristics. In this study, we directly compared two voltage-gated K+ channels, the mammalian RCK1 with the Drosophila Shab11, and correlated the specific amino acid content of their respective S4 regions with the distinct voltage-sensing properties they exhibit. We find that specific differences in the charge content of the S4 region are sufficient to account for the distinct gating valence of each channel. However, differences in residues inside the S4 region are not sufficient to account for each channel's characteristic voltage range of activation.