2024-03-28T09:22:58Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/551402016-02-17T05:51:58Zcom_10261_133com_10261_1col_10261_386
Substitutions of amino acids in the pore domain of homomeric α7 nicotinic receptors for analogous residues present in heteromeric receptors modify gating, rectification and binding properties
Criado, Manuel
Svobodová, Lucie
Mulet Soler, José
Sala, Francisco
Sala, Salvador
α7 neuronal nicotinic receptor
Homomeric
M2 segment
10 p., 6 figures and references.
We have studied the role of different amino acids in the M2 transmembrane domain of the α7 neuronal nicotinic receptor by mutating residues that differ from the ones located at the same positions in other α (α2-α10) or β (β2-β4) subunits. Our aim was to investigate the contribution of these amino acids to the peculiar kinetic and inward rectification properties that differentiate the homomeric α7 receptor from other nicotinic receptors. Mutations of several residues strongly modified receptor function. We found that Thr245 had the most profound effect when mutated to serine, an amino acid present in all heteromeric receptors composed of α and β subunits, by dramatically increasing the maximal current, decreasing the decaying rate of the currents and decreasing receptor rectification. Some mutants also showed altered agonist-binding properties as revealed by shifts in the dose-response curves for acetylcholine. We conclude that residues in the M2 segment and flanking regions contribute to the unusual properties of the α7 receptor, especially to its characteristic fast kinetic behavior and strong inward rectification and furthermore to the potency of agonists.
2012-08-28T11:51:33Z
2012-08-28T11:51:33Z
2011-10
artículo
Journal of Neurochemistry 119(1): 40-49 (2011)
0022-3042
http://hdl.handle.net/10261/55140
10.1111/j.1471-4159.2011.07398.x
1471-4159
eng
http://dx.doi.org/10.1111/j.1471-4159.2011.07398.x
closedAccess
Blackwell Publishing