A Structural Model of Fast Inactivation in Shaker KV Channels

Abstract

HCN channels possesses several residues that are absolutely conserved in the HCN family and that therefore, are potentially important for their unique gating. We individually mutated several of these conserved residues at the S4-S5 interface in the sea urchin HCN (spHCN) channel and expressed them in Xenopus laevis oocytes to measure the effects of each mutation using Voltage Clamp Fluorometry. Our results show that some residues at the S4-S5 interface are critical for normal S4 movement, while others are important to stabilize the gate or are involved in the coupling between S4 and the gate.