Non-Obligatory Gating of Kv7.1 Potassium Channel

Abstract

The response of voltage-dependent K+ (Kv) channels to a change in membrane voltage involves a molecular device, which couples voltage-driven conformational changes to gate opening and closing within the channel's conduction pathway. To further our understanding of the coupling choreography we have studied how changes in coupling strength instigate the Kv channel to open before and after voltage-sensor activation. We used single and double mutations in a Kv channel pore domain to analyze coupling sensitive sites. We observed in the mutational effects a correlation between coupling strength and non-obligatory Kv channel gating that is well described with a four-state allosteric gating model. Mapping the data onto known Kv channel structures showed that coupling-sensitive amino acid residues are strategically clustered to a small area between pore gate and the interface of pore and voltage sensors. We propose that the physical contact at the interface between voltage sensor and pore domain is an important determinant of altered coupling strengths leading to obligatory and non-obligatory Kv channel gating.