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.

Pulsed magnetic fields enhance the rate of recovery of damaged nerve excitability

“…Crush injury was performed as previously described [Mert et al, 2004]. Briefly, the left lateral thigh was shaved and prepped with Betadine solution.…”

“…After the wound was closed with 4-0 silk sutures, the animals were allowed to recover for 15-38 days. These time frames were based on our previous studies [Mert et al, 2004 and were chosen with the expectation that, at these post-surgical delays, possible PMF-induced changes on nerve regeneration could be determined. All surgical procedures were performed by the same researcher and conducted under sterile conditions using protocols approved by the animal care and use committee of our institution.…”

“…In preparation for sucrose-gap recordings [Mert et al, 2004] the animals were killed by cervical dislocation and their sciatic nerves were resected from the posterior thigh, desheathed (removal of circumferential sheath), and placed in oxygenated Krebs solution.…”

“…Regeneration or functional recovery of peripheral nerves following injury depends on the combined effects of several neuronal and non-neuronal factors [Schafer et al, 2006]. There are a large number of in vitro experimental studies that have suggested that after injury, incomplete functional peripheral nerve regeneration causes several electrophysiological abnormalities [Gordon et al, 1991;Mert et al, 2004;Mert, 2007]. Disturbed axonal excitability results in the inability to maintain conduction of a meaningful impulse train in the damaged nerve bundle [Mert, 2006[Mert, , 2007.…”

“…It is well known that voltagedependent ion channels are normally responsible for generation and propagation of action potentials along nerve fibers. As a result of injury/damage to myelinated nerve fibers, the distribution of voltage-dependent channels located along the axon is altered and thus the conduction of nerve action potentials is reduced or blocked [Rasband and Trimmer, 2001;Mert et al, 2004].…”