Ionic channels and signal conduction in single remyelinating frog nerve fibres.

1. Ionic currents have been measured in single demyelinated and remyelinating frog sciatic nerve fibres by means of the loose patch clamp technique. Axons were demyelinated by a surgical intraneural injection of lysolecithin and recovery was followed for up to 5 months. 2. Removal of myelin debris continued for the first 2 weeks post-injection. Proliferating Schwann cells were then seen within the lesion. As remyelination proceeded new nodes of Ranvier were formed in regions that previously were internodal. Original nodes, marking the transition from old to new myelin, could be identified at all stages. 3. Peak amplitudes of internodal transient inward Na+ currents were constant over the first 2 months and increased by about 60% after 5 months. Internodal currents in remyelinated axons were recorded after a second injection of lysolecithin to remove the thin myelin sheath. 4. Records from paranodal sites neighbouring transition nodes contained transient outward currents that were strongly voltage dependent and seemed to reflect activation of a very high density of Na+ channels just outside the patch. This sharp gradient in channel density at original nodes persisted throughout the period of remyelination studied suggesting that lateral diffusion from these sites is limited. These currents were never seen at internodal sites nor were they found at new nodes of Ranvier. 5. Paranodal inward current amplitudes in new nodes were similar to those in original (transition) nodes. 6. No transient inward Na+ currents were detected in Schwann cells adhering to demyelinated axons or free standing within the area of the lesion. 7. Conduction in single remyelinating fibres was studied by measuring membrane currents that flowed in response to an invading propagating action potential. At 2 weeks post-injection, prior to the formation of myelin, conduction was decremental, but activation of internodal Na+ channels allowed signals to penetrate further into the demyelinated zone than would have been possible by passive spread alone. After an additional 3 weeks, following formation of thin myelin sheaths, conduction was significantly improved and the fractional activation of Na+ channels was increased. 8. The results suggest that Na+ channels at new nodes of Ranvier come neither from original nodes nor from Schwann cells. They may represent a moderate aggregation of existing internodal channels. New nodes seem to possess a gradient of Na+ channel density that is much less steep than that at original nodes. Continuous conduction appears to be limited to short (approximately 0.2 mm) lengths of demyelinated axons.(ABSTRACT TRUNCATED AT 400 WORDS)