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The Journal of Neuroscience, May 15, 1999, 19(10):3701-3710

Nicotinic Acetylcholine Receptors Containing 7 Subunits Are Required for Reliable Synaptic Transmission In Situ

Karen T. Chang and Darwin K. Berg

Department of Biology, University of California, San Diego, La Jolla, California 92093

Nicotinic acetylcholine receptors containing 7 subunits are widely expressed in the nervous system. The receptors are cation-selective, relatively permeable to calcium, and avid binders of -bungarotoxin. Although the receptors can act both pre- and postsynaptically, their physiological significance is unclear. Using whole-cell patch-clamp analysis of chick ciliary ganglion neurons in situ, we show that the receptors are required for reliable synaptic transmission early in development. Stimulation of the presynaptic nerve root elicited a biphasic synaptic current, including a large rapidly decaying component generated by 7-containing receptors. Selective blockade of 7-containing receptors by perfusing the ganglion with -bungarotoxin induced failures in synaptic transmission. One-half of the ciliary neurons that were tested failed when stimulated synaptically at 1 Hz, and two-thirds failed at 25 Hz. Failing cells missed, on average, 80% of the trials during a test train of stimuli. The ability to fire synaptically evoked action potentials after toxin treatment was correlated positively with the amplitude of the remaining synaptic current, suggesting that 7-containing receptors were needed to augment synaptic responses. Consistent with patch-clamp analysis, toxin blockade reduced the amplitude of the synaptically evoked compound action potential in the postganglionic nerve; it also desynchronized the firing of the remaining units. Methyllycaconitine, another antagonist of 7-containing receptors, mimicked -bungarotoxin blockade. Toxin blockade had less impact on transmission in ganglia at the end of embryogenesis. The ability of the receptors to synchronize and sustain population firing, together with their ability to deliver calcium, may influence early developmental events such as target innervation and neuronal survival.

Key words: nicotinic; receptors; acetylcholine; ciliary; synaptic; transmission; neuronal; 7; -bungarotoxin; patch clamp; ganglion; calyx; postsynaptic

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19103701-10$05.00/0

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