Role of Potassium Channels in the Frequency-Dependent Activity of Regenerating Nerves

Abstract

After a peripheral nerve injury, ion channel organization and the electrical properties of nerve fibers drastically change during the regeneration process. The present study was designed to compare the frequency-dependent characteristics of regenerating nerves in the presence of 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The results showed that increasing the stimulus frequency produced a greater impulse blockade (frequency-dependent block – FDB) and distinct hyperpolarizing afterpotentials (HAPs) in regenerating nerves. In particular, regenerating sciatic nerves 15 days post-crush (dpc) were more sensitive to the frequency-dependent stimulations than 38-dpc and intact nerves in the presence or absence of drugs. The frequency-dependent effects of TEA on the compound action potentials (CAPs) appeared when TEA was applied to 4-AP-treated nerves. This shows that TEA-sensitive channels may not be masked by the myelin. 4-AP was here found to have more pronounced frequency-dependent effects on regenerating nerves than on intact nerves. Delayed depolarization (in 38-dpc: 22.6 ± 1.3 mV and 47.52 ± 3.63 ms, in intact: 12.0 ± 1.9 mV and 88.51 ± 4.72 ms) elicited by 4-AP resulted in an increase in FDBs and HAP amplitudes. These results suggest that 4-AP-sensitive channels may play important roles in frequency-dependent nerve conduction. Consequently, regenerating or myelin damaged nerves are more sensitive to repetitive firing with or without drug. An understanding of the frequency-dependent properties of regenerating nerves may be of value in the treatment of the nerve diseases.