Redox-sensitive extracellular gates formed by auxiliary beta subunits of calcium-activated potassium channels.
An important step to understanding ion channels is identifying the structural components that act as the gates to ion movement. Here we describe a new channel gating mechanism, produced by the beta3 auxiliary subunits of Ca2+-activated, large-conductance BK-type K+ channels when expressed with their pore-forming alpha subunits. BK beta subunits have a cysteine-rich extracellular segment connecting two transmembrane segments, with small cytosolic N and C termini. The extracellular segments of the beta3 subunits form gates to block ion permeation, providing a mechanism by which current can be rapidly diminished upon cellular repolarization. Furthermore, this gating mechanism is abolished by reduction of extracellular disulfide linkages, suggesting that endogenous mechanisms may regulate this gating behavior. The results indicate that auxiliary beta subunits of BK channels reside sufficiently close to the ion permeation pathway defined by the alpha subunits to influence or block access of small molecules to the permeation pathway.
Department of Anesthesiology, Washington University School of Medicine, Box 8054, St. Louis, Missouri 63110, USA.
Xu-Hui
XH
Zeng
Xiao-Ming
XM
Xia
Christopher J
CJ
Lingle
D000818:Animals; D018999:Charybdotoxin / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004229:Dithiothreitol / Q000737:chemistry; D004492:Edetic Acid / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008274:Magnesium / Q000378:metabolism; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D004220:Disulfides; D024681:Potassium Channels, Calcium-Activated; D021122:Protein Subunits; D018999:Charybdotoxin; D004492:Edetic Acid; D008274:Magnesium; D004229:Dithiothreitol