Lisa K Lyford

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The molecular mechanisms that couple agonist binding to the gating of Cys-loop ionotropic receptors are not well understood. The crystal structure of the acetylcholine (ACh) binding protein has provided insights into the structure of the extracellular domain of nicotinic receptors and a framework for testing mechanisms of activation. Key ligand binding(More)
Neuronal alpha(7) nicotinic acetylcholine receptors (nAChRs) are permeable to Ca(2+) and other divalent cations. We characterized the modulation of the pharmacological properties of nondesensitizing mutant (L(247)T and S(240)T/L(247)T) alpha(7) nAChRs by permeant (Ca(2+), Ba(2+), and Sr(2+)) and impermeant (Cd(2+) and Zn(2+)) divalent cations. alpha(7)(More)
Neuronal alpha7 nicotinic ACh receptors (nAChRs) are permeable to and modulated by Ca2+, Ba2+, and Sr2+. These permeant divalent cations interact with slowly desensitizing L247T alpha7 nAChRs to increase the potency and maximal efficacy of ACh, increase the efficacy of dihydro-beta-erythroidine (DHbetaE), and increase agonist-independent activity. Mutation(More)
alpha7 nicotinic receptors are highly permeable to Ca(2+) as well as monovalent cations. We extended the characterization of the Ca(2+) permeation of non-desensitizing chick alpha7 receptors (S240T/L247T alpha7 nAChRs) expressed in Xenopus oocytes by (1) measuring the concentration dependence of conductance under conditions in which Ca(2+) or Ba(2+) were(More)
The alpha7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that modulates neurotransmitter release in the central nervous system. We show here that functional, homo-oligomeric alpha7 nAChRs can be synthesized in vitro with a rabbit reticulocyte lysate translation system supplemented with endoplasmic reticulum microsomes, reconstituted(More)
A fundamental process in neurosecretion is desensitization, or a declining response to a stimulus. The response of chromaffin cells to continuous nicotinic stimulation, secretion of catecholamines, desensitizes within a few minutes. The neuropeptide substance P (SP) has been reported to prevent desensitization in culture dish experiments and to enhance(More)
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