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The Journal of Neuroscience, December 15, 1998, 18(24):10335-10344

Mammalian Nicotinic Receptors with alpha 7 Subunits That Slowly Desensitize and Rapidly Recover from alpha -Bungarotoxin Blockade

Javier Cuevas and Darwin K. Berg

Department of Biology, University of California, San Diego, La Jolla, California 92093-0357

One of the most abundant nicotinic receptors in the nervous system is a species that contains the alpha 7 gene product, rapidly desensitizes, and binds alpha -bungarotoxin with great affinity. The receptor has a high relative permeability to calcium and performs a variety of functions including presynaptic modulation of transmitter release and postsynaptic generation of synaptic currents. Fast excitatory transmission in mammalian intracardiac ganglia is mediated primarily by nicotinic receptors, and although intracardiac ganglion neurons express the alpha 7 gene, no toxin-sensitive response has been detected previously in them. We report here that whole-cell patch-clamp recordings from freshly dissociated intracardiac ganglion neurons reveal a nicotinic response that desensitizes slowly and is blocked by alpha -bungarotoxin in a rapidly reversible manner. The only rat gene previously thought capable of forming such receptors was alpha 9, but no evidence suggests that the alpha 9 gene is expressed in neurons. We find that reverse transcription (RT)-PCR detects alpha 7 but not alpha 9 mRNA in the ganglia. In addition, the pharmacology of the nicotinic response is typical of alpha 7-containing receptors but differs in several respects from that expected for alpha 9. Binding experiments with immunotethered receptors identifies a ganglionic species that contains the alpha 7 gene product. Moreover, intracellular perfusion of the cells with an anti-alpha 7 monoclonal antibody specifically reduces the amplitude of the toxin-sensitive response. The results indicate that alpha 7-containing receptors are responsible for the slowly desensitizing, toxin-reversible response and suggest that the receptors are modified in cell-specific ways to influence their functional properties.

Key words: nicotinic; receptors; acetylcholine; intracardiac ganglion; neuronal; alpha 7; alpha -bungarotoxin; patch clamp


Copyright © 1998 Society for Neuroscience  0270-6474/98/182410335-10$05.00/0


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