Mammalian Nicotinic Receptors with a7 Subunits That Slowly Desensitize and Rapidly Recover from a-Bungarotoxin Blockade

One of the most abundant nicotinic receptors in the nervous system is a species that contains the a7 gene product, rapidly desensitizes, and binds a-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 a7 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 a-bungarotoxin in a rapidly reversible manner. The only rat gene previously thought capable of forming such receptors was a9, but no evidence suggests that the a9 gene is expressed in neurons. We find that reverse transcription (RT)–PCR detects a7 but not a9 mRNA in the ganglia. In addition, the pharmacology of the nicotinic response is typical of a7-containing receptors but differs in several respects from that expected for a9. Binding experiments with immunotethered receptors identifies a ganglionic species that contains the a7 gene product. Moreover, intracellular perfusion of the cells with an anti-a7 monoclonal antibody specifically reduces the amplitude of the toxin-sensitive response. The results indicate that a7containing 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.