Maturation of mammalian myelinated fibers: changes in action-potential characteristics following 4-aminopyridine application

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Abstract
The effects of K channel blocking agents on action-potential waveform and firing characteristics of maturing rat sciatic nerve fibers were studied in vitro using compound action-potential and intra-axonal recording techniques. Application of 4-aminopyridine (4-AP) to the nerves led to an increased area under the monophasic compound action potential that was most pronounced in young animals. This effect gradually diminished during the course of maturation. The compound action potential of early myelinated nerves developed late negative components after 4-AP application that gave the response of rippled appearance. The late activity was the result of repetitive impulse generation in constituent fibers. Extracellular application of tetraethylammonium (TEA) ions or gallamine triethiodide was followed by a slight increase in duration of the whole-nerve response in young rats but not in older animals. Most (76.8%; n = 99) early myelinated axons (22-40 days postnatal) showed burst activity following 4-AP application, but only 15.8% (n = 76) of axons of more mature nerves gave rise to burst activity in the presence of 4-AP. The 4-AP-elicited burst activity, as determined by compound action-potential recordings, was present in Ca2+-free solution and in Cl--substituted solutions. Diphenylhydantoin (DPH) application (50 .mu.M) led to conduction slowing and reduction in both the primary negativity and the 4-AP-elicited late burst activity of the compound action potential. These results support the proposal that morphophysiological organization of K channels of myelinated axons early in development bears a closer resemblance to that of regenerated fibers than to normal mature myelinated fibers (25) and that the functional role of K channels of mammalian myelinated fibers is related to the stabilization of firing characteristics.