Dynamic rearrangement of the outer mouth of a K+ channel during gating.
With prolonged stimulation, voltage-activated K+ channels close by a gating process called inactivation. This inactivation gating can occur by two distinct molecular mechanisms: N-type, in which a tethered particle blocks the intracellular mouth of the pore, and C-type, which involves a closure of the external mouth. The functional motion involved in C-type inactivation was studied by introducing cysteine residues at the outer mouth of Shaker K+ channels through mutagenesis, and by measuring state-dependent changes in accessibility to chemical modification. Modification of three adjacent residues in the outer mouth was 130-10,000-fold faster in the C-type inactivated state than in the closed state. At one position, state-dependent bridging or crosslinking between subunits was also possible. These results give a consistent picture in which C-type inactivation promotes a local rearrangement and constriction of the channel at the outer mouth.
Liu
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Department of Neurobiology, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Jurman
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ME
Yellen
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D002460:Cell Line; D003432:Cross-Linking Reagents; D003545:Cysteine / Q000737:chemistry; D004229:Dithiothreitol / Q000494:pharmacology; D004553:Electric Conductivity; D004622:Embryo, Mammalian; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007668:Kidney; D046911:Macromolecular Substances; D008564:Membrane Potentials; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014162:Transfection
D003432:Cross-Linking Reagents; D046911:Macromolecular Substances; D015221:Potassium Channels; D008741:Methyl Methanesulfonate; D003545:Cysteine; D004229:Dithiothreitol