Theoretical Studies of Structure-Function Relationships in Kv Channels: Electrostatics of the Voltage Sensor

Voltage-gated ion channels mediate electrical excitability of cellular membranes. Reduced models of the voltage sensor of Kv channels produce insight into the electrostatic physics underlying the response of the S4 transmembrane domain to changes in membrane potential. By calculating the partition function computed from the electrostatic energy, I compute expectations of charge displacement, energetics, probability distributions of translation & rotation and Maxwell stress for S2, S3 & S4 arrangements. A ‘paddle’ model is rejected on electrostatic grounds. On the other hand, a ‘sliding helix’ model with three local counter-charges, a protein dielectric coefficient of 4 and a 2/3 interval of counter-charge positioning relative to the S4 α-helix period of positive residues is electrostatically reasonable, comparing well with Shaker. These ‘sliding helix’ models compare favorably with experimental results for mutant charge experiments on Shaker. Movies: https://sites.google.com/site/alexpeyserthesis