| Action of nicotine and analogs on acetylcholine receptors having mutations of transmitter-binding site residue αG153. | |
| | |
MedLine Citation:
|
PMID: 23277476 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
A primary target for nicotine is the acetylcholine receptor channel (AChR). Some of the ability of nicotine to activate differentially AChR subtypes has been traced to a transmitter-binding site amino acid that is glycine in lower affinity and lysine in higher affinity AChRs. We studied the effects of mutations of this residue (αG153) in neuromuscular AChRs activated by nicotine and eight other agonists including nornicotine and anabasine. All of the mutations increased the unliganded gating equilibrium constant. The affinity of the resting receptor (K(d)) and the net binding energy from the agonist for gating (ΔG(B)) were estimated by cross-concentration fitting of single-channel currents. In all but one of the agonist/mutant combinations there was a moderate decrease in K(d) and essentially no change in ΔG(B). The exceptional case was nicotine plus lysine, which showed a large, >8,000-fold decrease in K(d) but no change in ΔG(B). The extraordinary specificity of this combination leads us to speculate that AChRs with a lysine at position αG153 may be exposed to a nicotine-like compound in vivo. |
| | |
Authors:
|
Snehal Jadey; Prasad Purohit; Anthony Auerbach |
Related Documents
:
|
7549876 - Interaction of secb with intermediates along the folding pathway of maltose-binding pro... 12145316 - A structure-based mutational analysis of cyclophilin 40 identifies key residues in the ... 8704146 - Temperature-dependent increase in the dna-binding activity of a heat shock factor in an... 3782106 - Calmodulin-regulated binding of the 90-kda heat shock protein to actin filaments. 8800576 - Down-regulation of angiotensin ii receptors in hypertrophied human myocardium. 8725146 - Hepatic lipase mediates the uptake of chylomicrons and beta-vldl into cells via the ldl... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: The Journal of general physiology Volume: 141 ISSN: 1540-7748 ISO Abbreviation: J. Gen. Physiol. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-01-01 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985110R Medline TA: J Gen Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: 95-104 Citation Subset: IM |
Affiliation:
|
Department of Physiology and Biophysics, State University of New York, Buffalo, NY 14214. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Ablation of cardiac myosin-binding protein-C accelerates contractile kinetics in engineered cardiac ...
Next Document: Positions of ?2 and ?3 subunits in the large-conductance calcium- and voltage-activated BK potassium...