Journal of Neuroscience, Vol 9, 2902-2906, Copyright © 1989 by Society for Neuroscience
Neurotransmission regulates stability of acetylcholine receptors at the neuromuscular junction
OL Avila, DB Drachman and A Pestronk
Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21205.
The majority of acetylcholine receptors (AChRs) at normally innervated
neuromuscular junctions are stable, with a half-life averaging about 12 d
in most rodent muscles. Following denervation, the AChRs turn over much
more rapidly after a lag period. The mechanism by which motor nerves
normally maintain stabilization of junctional AChRs is not yet known. In
order to determine whether synaptic transmission plays a role in this
process, we have compared the effects of pre-and postsynaptic chloinergic
blockade with those of surgical denervation. 125l-alpha- bungarotoxin was
used to label junctional AChRs and follow their loss over time. Presynaptic
blockade of quantal ACh transmission was produced in the soleus (SOL) and
flexor digitorum brevis muscles of mice by repeated injections of type A
botulinum toxin. Postsynaptic blockade of quantal and nonquantal ACh
transmission was produced by continuous infusion of alpha-bungarotoxin in
the SOL. Our findings show that treatment with botulinum toxin resulted in
an accelerated loss of junctional AChRs that was similar to the effects of
surgical denervation, though briefly delayed in its onset. Treatment with
alpha- bungarotoxin produced an effect that was quantitatively equivalent
to the accelerated loss of junctional AChRs following surgical denervation,
with an identical time course. These results support the concept that
cholinergic transmission is a mediator of the neural control of stability
of junctional AChRs. The possibility that receptor stabilization may
represent a mechanism of long-term postsynaptic "memory" dependent on
neural transmission is discussed.
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