alpha7-Containing and non-alpha7-containing nicotinic receptors respond differently to spillover of acetylcholine.

摘要

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.