Expression and functional properties of α7 acetylcholine nicotinic receptors are modified in the presence of other receptor subunits.
Although α7 nicotinic receptors are predominantly homopentamers, previous reports have indicated that α7 and β2 subunits are able to form heteromers. We have studied whether other nicotinic receptor subunits can also assemble with α7 subunits and the effect of this potential association. Coexpression of α7 with α2, α3, or β4 subunits reduced to about half, surface α-bungarotoxin binding sites and acetylcholine-gated currents. This is probably because of inhibition of membrane trafficking, as the total amount of α7 subunits was similar in all cases and a significant proportion of mature α7 receptors was present inside the cell. Only β4 subunits appeared to directly associate with α7 receptors at the membrane and these heteromeric receptors showed some kinetic and pharmacological differences when compared with homomeric α7 receptors. Finally, we emulated the situation of bovine chromaffin cells in Xenopus laevis oocytes by using the same proportion of α3, β4, α5, and α7 mRNAs, finding that α-bungarotoxin binding was similarly reduced in spite of increased currents, apparently mediated by α3β4(α5) receptors.
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain. manuel.criado@umh.es
Manuel
M
Criado
Luis M
LM
Valor
José
J
Mulet
Susana
S
Gerber
Salvador
S
Sala
Francisco
F
Sala
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002038:Bungarotoxins / Q000493:pharmacokinetics; D002417:Cattle; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D019439:Chromaffin Cells; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D007814:Larva; D008082:Lipotropic Agents / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008845:Microinjections; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; D018678:Cholinergic Agents; C579167:Chrna7 protein, human; D007456:Iodine Isotopes; D008082:Lipotropic Agents; D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C485184:enhanced green fluorescent protein; C403530:nicotinic receptor alpha3beta4; D049452:Green Fluorescent Proteins; D002794:Choline; D000109:Acetylcholine