2014 Conway review lecture, Royal Academy of Medicine in Ireland: “S6, drugs and RCK and Bowl”.

BACKGROUND

The Conway Review Lecture is held annually by the Royal Academy of Medicine in Ireland Biomedical Sciences Section, to remember the life and scientific work of a world class Irish scientist, Professor Edward J Conway.

AIMS

This years lecture will focus on large conductance Ca2+ activated K+ (BK) channels and aims to describe how a combination of techniques can be used to unravel drug effects on ion channels at a molecular level.

METHODS

Experiments were performed using a range of techniques including patch clamp electrophysiology, mutagenesis, structural biology and mathematical modeling.

RESULTS

Our data suggest that the novel BK channel opener GoSlo-SR-5-6 mediates its effects via an interaction with 2 residues on S6 (S317 and I326) and a residue on the S4/S5 linker (L227).

CONCLUSIONS

We hypothesize that this novel opener activates BK channels by altering an interaction between the S4/S5 linker and the pore-forming S6 transmembrane helix.