Confocal calcium imaging reveals an ionotropic P2 nucleotide receptor in the paranodal membrane of rat Schwann cells

摘要

class="enumerated" style="list-style-type:decimal">The paranodal Schwann cell region is of major importance for the function of a myelinated axon. In the present study we searched for a possible ionotropic effect of extracellular ATP in this Schwann cell compartment.Whole-cell patch-clamp recordings from cultured rat Schwann cells revealed that ATP and 2′–3′-O-(4-benzoylbenzoyl)-adenosine 5′-triphosphate (BzATP) induced a non-specific cation current. The effect of ATP was much enhanced in a Ca²⁺- and Mg²⁺-free solution. ADP, UTP and α,β-methylene adenosine 5′-triphosphate (α,β-meATP) had no effect.Confocal Ca²⁺ imaging of myelinating Schwann cells in isolated rat spinal roots showed a BzATP-induced rise in the free intracellular Ca²⁺ concentration in the paranodal Schwann cell cytoplasm whereas α,β-meATP and 2-(methylthio)-adenosine 5′-triphosphate were without effect. In contrast to the known metabotropic effect of UTP on these Schwann cell regions, the BzATP-induced Ca²⁺ signal was not transient, was unaffected by depletion of intracellular Ca²⁺ stores and dependent on the presence of extracellular Ca²⁺.These results suggest that an ionotropic ATP receptor with electrophysiological and pharmacological characteristics of the P2X7 subtype of nucleotide receptors is functionally active in myelinating Schwann cells of peripheral nerves. Such a receptor might contribute to Schwann cell reactions in nerve injury or neuropathy.