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Properties of human glycine receptors containing the hyperekplexia mutation α1(K276E), expressed in Xenopus oocytes
Author(s) -
Lewis T. M.,
Sivilotti L. G.,
Colquhoun D.,
Gardiner R. M.,
Schoepfer R.,
Rees M.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.025bu.x
Subject(s) - strychnine , glycine receptor , glycine , receptor , mutant , xenopus , chemistry , mutation , endocrinology , biophysics , medicine , biology , microbiology and biotechnology , biochemistry , amino acid , gene
1 Inherited defects in human glycine receptors give rise to hyperekplexia (startle disease). We expressed human glycine receptors in Xenopus oocytes, in order to examine the pharmacological and single‐channel properties of receptors that contain a mutation, α1(K276E), associated with an atypical form of hyperekplexia. 2 Equilibrium concentration‐response curves showed that recombinant human α1(K276E)β receptors had a 29‐fold lower glycine sensitivity than wild‐type α1β receptors, and a greatly reduced Hill coefficient. The maximum response to glycine also appeared much reduced, whereas the equilibrium constant for the glycine receptor antagonist strychnine was unchanged. 3 Both wild‐type and mutant channels opened to multiple conductance levels with similar main conductance levels (33 pS) and weighted mean conductances (41.5 versus 49.8 pS, respectively). 4 Channel openings were shorter for the α1(K276E)β mutant than for the wild‐type α1β, with mean overall apparent open times of 0.82 and 6.85 ms, respectively. 5 The main effect of the α1(K276E) mutation is to impair the opening of the channel rather than the binding of glycine. This is shown by the results of fitting glycine dose‐response curves with particular postulated mechanisms, the shorter open times of mutant channels, the properties of single‐channel bursts, and the lack of an effect of the mutation on the strychnine‐binding site.