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 á7- and á3-containing nAChRs (á7-nAChRs and á3*-nAChRs). Elevating quantal content lengthened EPSC decay time and prolonged both the fast (á7-nAChR-mediated) and slow (á3*-nAChR-mediated) components of decay, even in the presence of acetylcholinesterase. Increasing quantal content also prolonged decay times of pharmacologically isolated á7-nAChR- and á3*-nAChR-EPSCs. The effect upon EPSC decay time of changing quantal content was 5-10 times more pronounced for á3*-nAChR- than á7-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 á3*-nAChR currents are prolonged at higher quantal content because of ACh spillover and postsynaptic potentiation (Hartzell et al., 1975), while á7-nAChR currents are prolonged probably for other reasons, e.g., increased occupancy of long channel open states. á3*-nAChRs report more spillover when á7-nAChRs are competitively blocked than under native conditions; this could be explained if á7-nAChRs buffer ACh and regulate its availability to activate á3*-nAChRs. Our results suggest that non-á7-nAChRs such as á3*-nAChRs may be suitable for paracrine nicotinic signaling but that á7-nAChRs may not be suitable. Our results further suggest that á7-nAChRs may buffer ACh and regulate its bioavailability.
Acetylcholine Aconitine