Activity-dependent extracellular potassium changes in unmyelinated versus myelinated areas in olfactory regions of the isolated female guinea-pig brain

The potassium released in the extracellular space during neuronal activity is rapidly removed by glia and neurons to maintain tissue homeostasis. Oligodendrocyte-derived myelin axonal coating contributes to potassium buffering and is therefore crucial to control brain excitability.

We studied activity-dependent extracellular potassium ([K⁺]_o) changes in the piriform cortex (PC), a region that features highly segregated bundles of myelinated and unmyelinated fibers. Four-aminopyridine (4AP; 50 μM) treatment or patterned high-frequency stimulations (hfST) were utilized to generate [K⁺]_o changes measured with potassium-sensitive electrodes in the myelinated lateral olfactory tract (LOT), in the unmyelinated PC layer I and in the myelinated deep PC layers in the ex vivo isolated guinea-pig brain.

Seizure-like events induced by 4AP are initiated by the abrupt [K⁺]_o rise in the layer I formed by unmyelinated fibers (Uva et al., 2017). Larger [K⁺]_o shifts occurred in unmyelinated layers compared to the myelinated LOT. LOT hfST that mimicks pre-seizure discharges also generated higher [K⁺]_o changes in unmyelinated PC layer I than in LOT and deep PC layers. The treatment with the Kir4.1 potassium channel blocker BaCl₂ (100 μM) enhanced the [K⁺]_o changes generated by hfST in myelinated structures.

Our data show that activity-dependent [K⁺]_o changes are intrinsically different in myelinated vs unmyelinated cortical regions. The larger [K⁺]_o shifts generated in unmyelinated structures may represent a vehicle for seizure generation.