α7-Containing and non-α7-containing nicotinic receptors respond differently to spillover of acetylcholine.
We explored whether nicotinic acetylcholine receptors (nAChRs) might participate in paracrine transmission by asking if they respond to spillover of ACh at a model synapse in the chick ciliary ganglion, where ACh activates diffusely distributed α7- and α3-containing nAChRs (α7-nAChRs and α3*-nAChRs). Elevating quantal content lengthened EPSC decay time and prolonged both the fast (α7-nAChR-mediated) and slow (α3*-nAChR-mediated) components of decay, even in the presence of acetylcholinesterase. Increasing quantal content also prolonged decay times of pharmacologically isolated α7-nAChR- and α3*-nAChR-EPSCs. The effect upon EPSC decay time of changing quantal content was 5-10 times more pronounced for α3*-nAChR- than α7-nAChR-mediated currents and operated over a considerably longer time window: ≈ 20 vs ≈ 2 ms. Control experiments rule out a presynaptic source for the effect. We suggest that α3*-nAChR currents are prolonged at higher quantal content because of ACh spillover and postsynaptic potentiation (Hartzell et al., 1975), while α7-nAChR currents are prolonged probably for other reasons, e.g., increased occupancy of long channel open states. α3*-nAChRs report more spillover when α7-nAChRs are competitively blocked than under native conditions; this could be explained if α7-nAChRs buffer ACh and regulate its availability to activate α3*-nAChRs. Our results suggest that non-α7-nAChRs such as α3*-nAChRs may be suitable for paracrine nicotinic signaling but that α7-nAChRs may not be suitable. Our results further suggest that α7-nAChRs may buffer ACh and regulate its bioavailability.
Department of Cell and Tissue Biology and Neuroscience Graduate Program, University of California, San Francisco, California 94143, USA.
Doychin
D
Stanchev
Peter B
PB
Sargent
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics; D019256:Cadmium Chloride / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002642:Chick Embryo; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D020916:Conotoxins / Q000494:pharmacology; D004456:Echothiophate Iodide / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D005726:Ganglia, Parasympathetic / Q000166:cytology; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D020916:Conotoxins; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C098872:alpha-conotoxin MII; C054634:methyllycaconitine; C012647:QX-314; D020866:omega-Conotoxin GVIA; D008012:Lidocaine; D004456:Echothiophate Iodide; D019256:Cadmium Chloride; D000109:Acetylcholine; D000157:Aconitine