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.
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.
Authors: B Kyle; E Bradley; S Ohya; G P Sergeant; N G McHale; K D Thornbury; M A Hollywood Journal: Am J Physiol Cell Physiol Date: 2011-08-03 Impact factor: 4.249
Authors: Timothy I Webb; Aravind Singh Kshatri; Roddy J Large; Adebola Morayo Akande; Subhrangsu Roy; Gerard P Sergeant; Noel G McHale; Keith D Thornbury; Mark A Hollywood Journal: Proc Natl Acad Sci U S A Date: 2015-02-04 Impact factor: 11.205
Authors: Subhrangsu Roy; Adebola Morayo Akande; Roddy J Large; Tim I Webb; Costin Camarasu; Gerard P Sergeant; Noel G McHale; Keith D Thornbury; Mark A Hollywood Journal: ChemMedChem Date: 2012-08-28 Impact factor: 3.466
Authors: Andrea L Meredith; Kevin S Thorneloe; Matthias E Werner; Mark T Nelson; Richard W Aldrich Journal: J Biol Chem Date: 2004-06-07 Impact factor: 5.157