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The Journal of Neuroscience, December 15, 1998, 18(24):10335-10344
Mammalian Nicotinic Receptors with 7 Subunits That Slowly
Desensitize and Rapidly Recover from -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 7 gene product, rapidly desensitizes,
and binds -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 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 -bungarotoxin in
a rapidly reversible manner. The only rat gene previously thought
capable of forming such receptors was 9, but no evidence suggests
that the 9 gene is expressed in neurons. We find that reverse
transcription (RT)-PCR detects 7 but not 9 mRNA in the
ganglia. In addition, the pharmacology of the nicotinic response is
typical of 7-containing receptors but differs in several respects
from that expected for 9. Binding experiments with immunotethered
receptors identifies a ganglionic species that contains the 7 gene
product. Moreover, intracellular perfusion of the cells with an
anti- 7 monoclonal antibody specifically reduces the amplitude of the
toxin-sensitive response. The results indicate that 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; 7; -bungarotoxin; patch clamp
Copyright © 1998 Society for Neuroscience 0270-6474/98/182410335-10$05.00/0
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