Conduction block in diabetic neuropathy.

Symmetric sensorimotor polyneuropathy is a common complication of diabetes. Sensory and motor evoked amplitudes and conduction velocities are reduced. Both demyelination and axon loss have been reported in pathologic studies. Conduction block (CB), a manifestation of segmental demyelination, has not been previously studied in diabetic neuropathy. We determined the prevalence of conduction block in patients with diabetes by analyzing electrodiagnostic data from 24 diabetics. Conduction block was defined as a greater than 20% drop in peak-to-peak amplitude, and a less than 15% change in negative-peak duration between proximal and distal stimulation sites. A total of 76 nerve segments were studied. The criteria for conduction block were met in only 6 segments in 6 patients. The mean decrease in peak-to-peak amplitude between stimulation sites was 28% (range 21% to 40%). We conclude that conduction block over long nerve segments is uncommon in diabetic neuropathy, and, if present, suggests that other causes for neuropathy in diabetic patients should be sought.

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.