Neurotransmission regulates stability of acetylcholine receptors at the neuromuscular junction.
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.
Avila
O L
OL
Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21205.
Drachman
D B
DB
Pestronk
A
A
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009407:Nerve Block; D009469:Neuromuscular Junction / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission
D002038:Bungarotoxins; D011950:Receptors, Cholinergic; D001905:Botulinum Toxins