Uptake of potassium by nonmyelinating Schwann cells induced by axonal activity.

1. The electrophysiological properties of the rabbit vagus nerve (membrane potential, compound action potentials, and afterpotentials) and potassium accumulation were measured simultaneously during low-frequency stimulation (LFS) (0.5 and 1 Hz) by using a modified sucrose-gap apparatus and potassium-sensitive microelectrodes (KSM). 2. During LFS at 0.5 and 1 Hz, the concentration of K+ in the extracellular space ([K+]c) increased in approximately 30 s to a maximal level that was 0.6 and 1.5 mM, respectively, above the resting concentration. Concomitantly the preparation developed an ouabain-sensitive hyperpolarization. 3. The compound action potential (CAP) was followed by a fast hyperpolarizing afterpotential (fHAP), a depolarizing afterpotential (DAP), and a slow hyperpolarizing afterpotential (sHAP). During LFS the characteristics of all these afterpotentials were profoundly modified. In parallel to the increase in [K+]e, the fHAP was decreased and the amplitude of the DAP was dramatically enhanced. Furthermore, the sHAP which had a duration of < 1 s when it followed a single CAP, turned into a ouabain-sensitive hyperpolarization (indicating that it was generated by the electrogenic Na(+)-K+ pump) that lasted several minutes. 4. The application of external Ba2+ produced a hyperpolarizing sag on the sHAP following a single isolated CAP. During LFS, Ba2+ enhanced the build-up of the DAP, raised the maximal level of [K+]e, and increased the activity-induced ouabain-sensitive hyperpolarization. 5. The increase by Ba2+ of the activity-induced hyperpolarization shifted the spikes from both myelinated and nonmyelinated fibers toward a more negative potential but did not increase their amplitude, indicating that this Ba(2+)-induced hyperpolarization originated from an extra-axonal source, presumably the Schwann cells. 6. It is proposed that the electrogenic activity of the Na(+)-K+ pump was enhanced in Schwann cells situated near active axons. This hyperpolarization was, however, not recorded in normal conditions because it was fully short-circuited by a K+ influx through Ba(2+)-sensitive channels. 7. Our results lead to the hypothesis that the Na(+)-K+ pump of the nonmyelinating Schwann cells is important in the mechanisms maintaining the homeostasis of K+ in the axonal microenvironment. They show that the Na(+)-K+ pump contributes to the K+ buffering not only by actively pumping K+ but also by generating a hyperpolarization that drives a passive K+ influx through Ba(2+)-sensitive K+ channels.