TRPA1 REGULATES DYNAMIC COMPENSATORY POTASSIUM CHANNEL INTERPLAY IN OLIGODENDROCYTES

Potassium channels in oligodendrocytes are essential for potassium buffering and myelin integrity, yet how distinct channel populations are coordinated across brain regions remains unclear. We performed whole-cell patch-clamp recordings from mature oligodendrocytes (MOLs) in the corpus callosum (white matter, WM) and motor cortex (grey matter, GM) and applied pharmacological manipulations to dissect channel contributions. In GM MOLs, blockade of inwardly rectifying potassium (Kir) channels with barium (100 μM) significantly reduces potassium conductance, whereas it has minimal effect in WM MOLs, indicating region-specific differences in Kir expression or function. Activation of the Transient Receptor Potential Ankyrin 1 (TRPA1) channel with agonists inhibits oligodendroglial potassium conductance. In TRPA1 global knockout mice (gKO), resting potassium conductance is markedly reduced at postnatal days P12–P18 and returns to wild-type levels at P18–P25. Immunohistochemical analyses show a developmental decrease in specific Kir channel expression in gKO at P14 followed by increased expression at P30, alongside reduced myelin basic protein (MBP) levels in gKO at P21 that recover by P30. Ongoing work will determine how TRPA1 regulates oligodendroglial potassium channel expression and conductance across regions and developmental stages and how these mechanisms influence myelin stability. Together, these findings identify TRPA1 as a key regulator of oligodendroglial potassium channel function with implications for activity-dependent myelin vulnerability.