BPS2026 – Molecular and electrophysiological characterization of nociceptive Schwann cells

Sensory Schwann cells in the skin ensheathe free nociceptive nerve endings and directly excite them to convey noxious mechanical stimuli, however, the ion channels expressed in these cells and their roles in nociception remains unexplored. In the present study, we isolated primary cutaneous Schwann cells expressing Tomato using the Sox10 promoter from hind paw mouse skin, maintained them in culture for 2–6 days, and used patch-clamp recordings to record macroscopic ionic currents. Mechanical stimulation (1 to 7 micron displacement) of isolated cells evoked inward currents when voltage was clamped at negative values. In current-clamp experiments, cells typically exhibited resting membrane potentials around −45 to −55 mV and mechanical stimulation evoked 20–30 mV depolarizations. Mechanosensitive currents in sensory Schwann cells exhibited inactivating and non-inactivating components in response to 200 ms displacement, with the inactivating component decaying in 10–20 ms, notably slower than reported for Piezo2 channels. We also observed robust voltage-activated outward currents in nociceptive Schwann cells, arising from voltage-activated potassium (Kv) channels in the Kv1 family, as confirmed single cell RNA seq and suppression of outward currents by the Kv1 inhibitor, α - Dendrotoxin . In a minority of cells, we measured voltage-activated currents carried by calcium ions. We are currently using genetic, pharmacological and biophysical approaches to define the molecular identity of mechanosensitive and voltage-activated ion channels expressed in nociceptive Schwann cells so their roles in sensing mechanical pain can be further explored.