Vol. 286, Issue 1, 311-320, July 1998

5 Subunit Alters Desensitization, Pharmacology, Ca⁺⁺ Permeability and Ca⁺⁺ Modulation of Human Neuronal 3 Nicotinic Receptors¹

Volodymyr Gerzanich, Fan Wang, Alexander Kuryatov and Jon Lindstrom

Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania

Functional effects of human 5 nicotinic ACh receptor (AChR) subunits coassembled with 3 and 2 or with 3 and 4 subunits, were investigated in Xenopus oocytes. The presence of 5 subunits altered some properties of both 3 AChRs and differentially altered other properties of 32 AChRs vs. 34 AChRs. 5 subunits increased desensitization and Ca⁺⁺ permeability of all 3 AChRs. The Ca⁺⁺ permeabilities of both 325 and 345 AChRs were comparable to that of 7 AChRs. As we have shown previously, 5 subunits increased the ACh sensitivity of 32 AChRs 50-fold but had little effect on 34 AChRs. 5 caused only subtle changes in the activation potencies of 3 AChRs for nicotine, cytisine and 1,1-dimethyl-4-plenylpiperazinium (DMPP). However, 5 increased the efficacies of nicotine and DMPP on 32 AChRs but decreased them on 34 AChRs. Immunoisolation of cloned human AChRs expressed in oocytes showed that 5 efficiently coassembled with 3 plus 2 and/or 4 subunits. As expected, human AChRs immunoisolated from SH-SY5Y neuroblastoma cells showed that AChRs containing 3 and probably 5 subunits were present, but 4 AChRs were not. In brain, by contrast, 42 AChRs were shown to predominate over 3 AChRs. Some of the brain 42 AChRs were found to contain 5 subunits.