Stanchev_2011_J.Neurosci_31_14920

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 alpha7- and alpha3-containing nAChRs (alpha7-nAChRs and alpha3*-nAChRs). Elevating quantal content lengthened EPSC decay time and prolonged both the fast (alpha7-nAChR-mediated) and slow (alpha3*-nAChR-mediated) components of decay, even in the presence of acetylcholinesterase. Increasing quantal content also prolonged decay times of pharmacologically isolated alpha7-nAChR- and alpha3*-nAChR-EPSCs. The effect upon EPSC decay time of changing quantal content was 5-10 times more pronounced for alpha3*-nAChR- than alpha7-nAChR-mediated currents and operated over a considerably longer time window: approximately 20 vs approximately 2 ms. Control experiments rule out a presynaptic source for the effect. We suggest that alpha3*-nAChR currents are prolonged at higher quantal content because of ACh spillover and postsynaptic potentiation (Hartzell et al., 1975), while alpha7-nAChR currents are prolonged probably for other reasons, e.g., increased occupancy of long channel open states. alpha3*-nAChRs report more spillover when alpha7-nAChRs are competitively blocked than under native conditions; this could be explained if alpha7-nAChRs buffer ACh and regulate its availability to activate alpha3*-nAChRs. Our results suggest that non-alpha7-nAChRs such as alpha3*-nAChRs may be suitable for paracrine nicotinic signaling but that alpha7-nAChRs may not be suitable. Our results further suggest that alpha7-nAChRs may buffer ACh and regulate its bioavailability.