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We have identified a means by which agonist-evoked responses of nicotinic receptors can be conditionally eliminated. Modification of α7L119C mutants by the sulfhydryl reagent 2-aminoethyl methanethiosulfonate (MTSEA) reduces responses to acetylcholine (ACh) by more than 97%, whereas corresponding mutations in muscle-type receptors produce effects that(More)
Although α7 nicotinic acetylcholine receptors are considered potentially important therapeutic targets, the development of selective agonists has been stymied by the α7 receptor's intrinsically low probability of opening (P(open)) and the concern that an agonist-based therapeutic approach would disrupt endogenous cholinergic function. Development of α7(More)
Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (agonists, partial agonists, competitive(More)
Knowledge of the cellular events that underlie initiation of outgrowth is crucial to understanding regulation of development and regeneration of the nervous system. This study utilized a culture preparation in which growth cone formation could be studied independent of cellular responses to the presence of conditioning factors. Identified neurons were(More)
α7 nicotinic acetylcholine receptors (nAChRs) have been a puzzle since their discovery in brain and non-neuronal tissues. Maximal transient probability of an α7 nAChR being open with rapid agonist applications is only 0.002. The concentration dependence of α7 responses measured from transfected cells and Xenopus laevis oocytes shows the same disparity in(More)
We have shown previously that a highly conserved Tyr in the nicotinic acetylcholine receptor (nAChR) ligand-binding domain (LBD) (alpha7 Tyr188 or alpha4 Tyr195) differentially regulates the activity of acetylcholine (ACh) and the alpha7-selective agonist 3-(4-hydroxy,2-methoxybenzylidene)anabaseine (4OH-GTS-21) in alpha4beta2 and alpha7 nAChR. In this(More)
Restricted repetitive behaviors (stereotypy, compulsions, rituals) are diagnostic for autism spectrum disorder and common in related neurodevelopmental disorders. Despite their prevalence in clinical populations, underlying mechanisms associated with the development of these behaviors remain poorly understood. We examined the role of the indirect basal(More)
A large number of structurally diverse ligands have been produced to selectively target α7 nicotinic acetylcholine receptors (nAChRs). We applied the method of scanning cysteine accessibility mutations (SCAM) to the ligand-binding domain of the α7 nAChR to identify subdomains of particular importance to the binding and subsequent activation by select(More)
Accumulating evidence indicates that cytosolic calcium levels regulate growth cone motility and neurite extension. The purpose of this study was to determine if intracellular calcium levels also influence the initiation of neurite extension induced by growth-promoting factors. An in vitro preparation of axotomized neurons that can be maintained in the(More)