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

Peter Grafe, Christian Mayer, Tomoko Takigawa, Martin Kamleiter and Rita Sanchez-Brandelik

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 ,-methylene adenosine 5'-triphosphate (,-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 ,-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.

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