Rapid activation of presynaptic nicotinic acetylcholine receptors by nerve-released transmitter


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    Present address: Division of Oral Biology, S-501, University of California, San Francisco, San Francisco, CA 94143–0512, USA

: Dr Peter B. Sargent, *present address below.
E-mail: sargent@itsa.ucsf.edu


Nicotine's ability to enhance neurotransmitter release has implicated presynaptic nicotinic acetylcholine receptors (nAChRs) in synaptic modulation, but there are few examples where presynaptic nAChRs are known to be activated by nerve-released transmitter. We searched for endogenous activation of presynaptic nAChRs in the calyceal nerve terminals of the chick ciliary ganglion by imaging presynaptic calcium transients using dextran-coupled indicator dyes. The amplitude of Ca2+ signals recorded in individual nerve terminals was frequency dependent over 2–50 Hz. Calcium transients evoked by stimulation of the preganglionic nerve were significantly reduced (≈10–15%) by the nonspecific nAChR antagonist d-tubocurarine (d-TC; 100 µm) and the α7-specific antagonist methyllycaconitine (20–50 nm) but were not affected by 10 µm dihydro-β-erythroidine, which should inhibit several non-α7 nAChRs. Feedback was rapid and did not require a stimulation-dependent build-up of transmitter, as d-TC and MLA reduced the amplitude of the first calcium transient in a 2-Hz train. Choline is an agonist at α7 nAChRs but is not the sole agonist in this system, as inhibition of acetylcholinesterase by echothiophate failed to reduce calcium transients. These results show that nerve-released acetylcholine (ACh) feeds back onto presynaptic α7 nAChRs to enhance calcium signals within the terminal. This feedback may help maintain the high rate of transmission at this cholinergic synapse.