Endoneurial potassium is increased and enhances spontaneous activity in regenerating mammalian nerve fibers—implications for neuropathic positive symptoms

The endoneurial fluid potassium [K⁺]_e has potent effects on membrane potential and excitability but direct measurements have not been reported. The [K⁺]_e was measured with K⁺ ion‐sensitive microelectrodes in normal, demyelinated, and regenerating rat peripheral nerve fibers. The mean value in normal nerve was 3.7 mM. The [K⁺]_e was consistently elevated in regenerating nerves and infrequently elevated in demyelinated nerves. The time course of [K⁺]_e was studied in the left tibial nerve of 22 rats 2 days to 3 months in the extended crush model. The [K⁺]_e was increased and peaked in the first 2 weeks, with a progressive decline toward control values after that. Single fiber recordings were made from the tibial division of the sciatic nerve in 13 animals. The mean number of single fibers studied per rat was 55.5 (SD 24.6). Spontaneous activity (SA) was present in all regenerating nerves and was maximal in the first 2–4 weeks. Endoneurial K⁺ was further increased by intraarterial injection of potassium into the saphenous artery. Spontaneous activity was enhanced when [K⁺]_e began to rise; there were further superimposed bursts of SA with the administration of additional boluses. These findings suggest that [K⁺]_e increase is a factor in enhancing SA in damaged nerve fibers.