Open AccessMutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal alpha 7 nicotinic receptor.
Author(s) -
Daniel Bertrand,
JeanLuc Galzi,
Anne DevillersThiéry,
Sonia Bertrand,
Jean Pierre Changeux
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.15.6971
Subject(s) - nicotinic acetylcholine receptor , chemistry , biophysics , calcium , alpha 4 beta 2 nicotinic receptor , receptor , acetylcholine receptor , nicotinic agonist , biochemistry , biology , organic chemistry
The relative permeability for sodium, potassium, and calcium of chicken alpha 7 neuronal nicotinic receptor was investigated by mutagenesis of the channel domain M2. Mutations in the "intermediate ring" of negatively charged residues, located at the cytoplasmic end of M2 (site 1), reduce calcium permeability without significantly modifying other functional properties (activation and desensitization) of the receptor; a similar change of ion selectivity is also noticed when mutations at site 1 are done in the context of a receptor mutant that conducts ions in a desensitized state. Moreover, mutations of two adjacent rings of leucines at the synaptic end of M2 (site 2) have multiple effects. They abolish calcium permeability, increase the apparent affinity for acetylcholine by 10- to 100-fold, augment Hill numbers (up to 4.6-5.0) of acetylcholine dose-response relationships, slow rates of ionic response onset, and lower the extent of desensitization. Mutations at these two topographically distinct sites within M2 selectively alter calcium transport without affecting the relative permeabilities for sodium and potassium.