Abstract
Functional effects of human α5 nicotinic ACh receptor (AChR) subunits coassembled with α3 and β2 or with α3 and β4 subunits, were investigated in Xenopus oocytes. The presence of α5 subunits altered some properties of both α3 AChRs and differentially altered other properties of α3β2 AChRs vs. α3β4 AChRs. α5 subunits increased desensitization and Ca++permeability of all α3 AChRs. The Ca++ permeabilities of both α3β2α5 and α3β4α5 AChRs were comparable to that of α7 AChRs. As we have shown previously, α5 subunits increased the ACh sensitivity of α3β2 AChRs 50-fold but had little effect on α3β4 AChRs. α5 caused only subtle changes in the activation potencies of α3 AChRs for nicotine, cytisine and 1,1-dimethyl-4-plenylpiperazinium (DMPP). However, α5 increased the efficacies of nicotine and DMPP on α3β2 AChRs but decreased them on α3β4 AChRs. Immunoisolation of cloned human AChRs expressed in oocytes showed that α5 efficiently coassembled with α3 plus β2 and/or β4 subunits. As expected, human AChRs immunoisolated from SH-SY5Y neuroblastoma cells showed that AChRs containing α3 and probably α5 subunits were present, but α4 AChRs were not. In brain, by contrast, α4β2 AChRs were shown to predominate over α3 AChRs. Some of the brain α4β2 AChRs were found to contain α5 subunits.
Footnotes
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Send reprint requests to: Dr. Jon Lindstrom, 217 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104-6074.
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↵1 Research in the laboratory of J.L. is supported by grants from the NIH (NS11323), the Smokeless Tobacco Research Council, Inc., The Council for Tobacco Research–USA, Inc., and the Muscular Dystrophy Association.
- Abbreviations:
- AChR
- acetylcholine receptor
- mAb
- monoclonal antibody
- DMPP
- 1,1-dimethyl-4-phenylpiperazinium
- Received November 6, 1997.
- Accepted March 2, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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α5 Subunit Alters Desensitization, Pharmacology, Ca++ Permeability and Ca++ Modulation of Human Neuronal α3 Nicotinic Receptors
