The voltage sensor domain (VSD) of ion channels senses changes in transmembrane potential and triggers opening and closing of the channel's pore.The conformational change of the VSD is transduced to the channels pore through flexible linkers which ultimately control the VSD’s resting and activated conformation. In this project, we have investigated the influence of both length and composition of the N- (S3S4) and C-terminal (S4S5) VSD linkers on BK channel gating and activation.We find that only the length but not the composition of the N-terminal linker controls the conformational space available to the VSD, with profound effects on gating kinetics. The C-terminal linker is responsible for transmitting the conformational change to the pore, and even minor mutations significantly diminish voltage sensitivity. Some degree of voltage sensitivity, however, is retained, which is in accordance with recently available structural data

In voltage gated ion channels, the voltage sensor domain (VSD) reacts to changes in the surrounding electric field and triggers opening and closing of the ion channel's pore. In this project, I have attempted mimicking the conformational transitions of the VSD by the application of mechanical fore to specific parts of the channel protein. This has been achieved by attaching a micron-sized probe to engineered attachment sites at the extracellular interface of the VSD. Several dataset obtained in the course of this project indicate that this kind of manipulation does facilitate channel opening by reducing the amount of voltage required to open the channel for the system under investigation, BK channel from mouse. Data, however, is still sparse and indirect effects, for example through deformation of the membrane instead of direct manipulation of the channel, cannot be ruled out entirely