Characterization of mechanosensitive and voltage-activated ion channels in nociceptive Schwann cells.

Abstract

Chronic pain is a pressing worldwide health problem, affecting nearly one fifth of the population. Our sense of pain has traditionally been thought of as arising entirely by the activation of nociceptive nerve endings in the skin, which are metabolically supported and protected by surrounding Schwann cells. However, it has recently been shown that a molecularly and morphologically unique Schwann cell subtype at the dermal-epidermal border of the skin exhibits mechanosensitive properties and may initiate mechanical pain. The ion channels expressed in these Schwann cells and their electrophysiological properties remain to be defined. 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 of isolated cells at negative holding potentials evoked inward currents, confirming the expression of mechanosensitive ion channels. We also observed robust voltage-activated currents in nociceptive Schwann cells that only slowly inactivate, likely arising from voltage-activated potassium (Kv) channels in the Kv1 family. In some cells we also measured voltage-activated currents likely arising from a relatively non-selective cation channel. 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.