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Query: UMLS:C0848283 (rundown)
 502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha 7-Nicotinic acetylcholine receptors (alpha 7-nAChRs) are broadly distributed in the central nervous system, where they play important roles in chemical and electrical signaling, and perhaps in neurite outgrowth, synaptic plasticity, and neuronal death/survival. To help elucidate their normal and pathophysiological roles, we have heterologously expressed human alpha 7-nAChR in transfected SH-EP1 human epithelial cells. Reverse transcription-polymerase chain reaction and mRNA fluorescence in situ hybridization analyses demonstrate expression of human alpha 7 subunits as messenger RNA. Patch-clamp recordings exploiting a novel strategy to prevent functional rundown of whole-cell peak current responses to repeated acute challenges with nicotinic agonists show successful expression of functional alpha 7-nAChR that mediate inward currents characterized by rapid phases of activation and inactivation. Concentration-response curves show that nicotine, acetylcholine, and choline are efficacious agonists at human alpha 7-nAChRs. Current-voltage relationships show inward rectification for agonist-induced currents. Human alpha 7-nAChRs exhibit some sensitivity to alpha 7-nAChR antagonists alpha-bungarotoxin (Bgt) or methyllycaconitine (MLA) when applied coincidentally with agonist, but much higher affinity block occurs when cells and alpha 7-nAChRs are pre-exposed to antagonists for 2 min before challenge with agonist. Both Bgt and MLA are competitive inhibitors of alpha 7-nAChR function. Whole-cell current peak amplitudes and half-times for inactivation of alpha 7-nAChR functional responses to nicotine are dramatically reduced in the absence of extracellular Ca2+, suggestive of high Ca2+ permeability of the alpha 7-nAChR channel. Thus, heterologously expressed human alpha 7-nAChR in mammalian cells have properties of native alpha 7-nAChR or of alpha 7-nAChR heterologously expressed in other systems and serve as excellent models for studies of molecular bases of alpha 7-nAChR function.
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PMID:Functional properties of homomeric, human alpha 7-nicotinic acetylcholine receptors heterologously expressed in the SH-EP1 human epithelial cell line. 1262 41

Naturally expressed nicotinic acetylcholine receptors (nAChR) containing alpha4 subunits (alpha4*-nAChR) in combination with beta2 subunits (alpha4beta2-nAChR) are among the most abundant, high-affinity nicotine binding sites in the mammalian brain. beta4 subunits are also richly expressed and colocalize with alpha4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, alpha4beta4-nAChR also may exist and play important functional roles. In this study, properties were determined of human alpha4beta2- and alpha4beta4-nAChR heterologously expressed de novo in human SH-EP1 epithelial cells. Whole-cell currents mediated via human alpha4beta4-nAChR have approximately 4-fold higher amplitude than those mediated via human alpha4beta2-nAChR and exhibit much slower acute desensitization and functional rundown. Nicotinic agonists induce peak whole-cell current responses typically with higher functional potency at alpha4beta4-nAChR than at alpha4beta2-nAChR. Cytisine and lobeline serve as full agonists at alpha4beta4-nAChR but are only partial agonists at alpha4beta2-nAChR. However, nicotinic antagonists, except hexamethonium, have comparable affinities for functional alpha4beta2- and alpha4beta4-nAChR. Whole-cell current responses show stronger inward rectification for alpha4beta2-nAChR than for alpha4beta4-nAChR at a positive holding potential. Collectively, these findings demonstrate that human nAChR beta2 or beta4 subunits can combine with alpha4 subunits to generate two forms of alpha4*-nAChR with distinctive physiological and pharmacological features. Diversity in alpha4*-nAChR is of potential relevance to nervous system function, disease, and nicotine dependence.
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PMID:Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors. 1682 97