alpha 5 Subunit alters desensitization, pharmacology, Ca++ permeability and Ca++ modulation of human neuronal alpha 3 nicotinic receptors.
Functional effects of human alpha 5 nicotinic ACh receptor (AChR) subunits coassembled with alpha 3 and beta 2 or with alpha 3 and beta 4 subunits, were investigated in Xenopus oocytes. The presence of alpha 5 subunits altered some properties of both alpha 3 AChRs and differentially altered other properties of alpha 3 beta 2 AChRs vs. alpha 3 beta 4 AChRs. alpha 5 subunits increased desensitization and Ca++ permeability of all alpha 3 AChRs. The Ca++ permeabilities of both alpha 3 beta 2 alpha 5 and alpha 3 beta 4 alpha 5 AChRs were comparable to that of alpha 7 AChRs. As we have shown previously, alpha 5 subunits increased the ACh sensitivity of alpha 3 beta 2 AChRs 50-fold but had little effect on alpha 3 beta 4 AChRs. alpha 5 caused only subtle changes in the activation potencies of alpha 3 AChRs for nicotine, cytisine and 1,1-dimethyl-4-plenylpiperazinium (DMPP). However, alpha 5 increased the efficacies of nicotine and DMPP on alpha 3 beta 2 AChRs but decreased them on alpha 3 beta 4 AChRs. Immunoisolation of cloned human AChRs expressed in oocytes showed that alpha 5 efficiently coassembled with alpha 3 plus beta 2 and/or beta 4 subunits. As expected, human AChRs immunoisolated from SH-SY5Y neuroblastoma cells showed that AChRs containing alpha 3 and probably alpha 5 subunits were present, but alpha 4 AChRs were not. In brain, by contrast, alpha 4 beta 2 AChRs were shown to predominate over alpha 3 AChRs. Some of the brain alpha 4 beta 2 AChRs were found to contain alpha 5 subunits.
Gerzanich
V
V
Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, USA.
Wang
F
F
Kuryatov
A
A
Lindstrom
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D009474:Neurons / Q000737:chemistry*; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry; D014981:Xenopus
D000911:Antibodies, Monoclonal; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; C082748:epibatidine; D002118:Calcium