Functional properties of neuronal nicotinic acetylcholine receptor channels expressed in transfected human cells.
To study how subunit composition affects the functional properties of neuronal nicotinic acetylcholine receptors (nAChRs), we examined the behaviour of acetylcholine (ACh)-induced single-channel currents in human BOSC 23 cells transiently transfected with various subunit cDNA combinations. For all nAChRs examined (chick and rat alpha 3 beta 4, chick alpha 3 beta 2, alpha 4 beta 2, alpha 7 and alpha 8), expression levels were high enough to allow measurements of acetylcholine-evoked whole-cell currents and nicotine-elicited Ca2+ transients as well as the functional characterization of nAChR channels. Unitary acetylcholine-evoked events of alpha 8 nAChR had a slope conductance of 23 pS, whereas two conductance classes (19-23 and 32-45 pS) were identified for all other nAChR channels. The mean channel open times were significantly longer for homomeric alpha 7 and alpha 8 nAChRs (6-7 ms) than for heteromeric nAChRs (1-3 ms), with the exception of alpha 3 beta 4 nAChRs (8.4 ms for rat, 7 ms for chick). At least two species of heterologously expressed nAChRs (alpha 3 beta 4 and alpha 3 beta 2) exhibited single-channel characteristics similar to those reported for native receptors. The variety of nAChR channel conductance and kinetic properties encountered in human cells transfected with nAChR subunits contributes to the functional diversity of nAChRs in nerve cells.
Ragozzino
D
D
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Medicina Sperimentale e Patologia, Università di Roma, Italy.
Fucile
S
S
Giovannelli
A
A
Grassi
F
F
Mileo
A M
AM
Ballivet
M
M
Alemà
S
S
Eusebi
F
F
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002645:Chickens; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D011978:Receptors, Nicotinic; D000109:Acetylcholine