ATP affects both axons and Schwann cells of unmyelinated C fibres

Recent studies indicate that effects of ATP on unmyelinated afferent nerve fibres contribute to the transduction of nociceptive and nonnociceptive sti muli. In the present study, effects of ATP were studied on axons and Schwan n cells of C fibres in isolated rat vagus nerves. A combination of a comput erised threshold tracking technique with photometric and confocal measureme nts of the free intracellular Ca2+ concentration revealed differences in th e effect of ATP and related compounds. Pyridoxal-phosphate-6-azophenyl-2',5 '-disulphonic acid (iso-PPADS, an antagonist of ionotropic P2X receptors) c ompletely blocked the excitatory effect of alpha,beta -meATP on unmyelinate d axons, whereas the effects of ATP and 2-Cl-ATP were only slightly changed . Moreover, the threshold lowering effects of ATP and 2-Cl-ATP, but not of alpha,beta -meATP, were accompanied by intracellular Ca2+ transients. In co nfocal imaging experiments, the lectin IB4 was used to identify unmyelinate d nerve fibres and their ensheathing Schwann cells. The Schwann cells were identified as the cellular elements underlying ATP induced Ca2+ transients. In addition, an increase in axonal excitability of C fibres was seen durin g a rise in [Ca2+](i) induced by inhibition of the endoplasmic Ca2+ ATPase with cyclopiazonic acid. These data show that an increase of the extracellu lar ATP concentration in an intact peripheral nerve trunk activates both ax ons and Schwann cells. It appears that P2 nucleotide receptors on Schwann c ells may contribute to the excitatory effect of ATP observed on unmyelinate d, including nociceptive, axons. (C) 2001 Elsevier Science B.V. Published b y Elsevier Science B.V. All rights reserved.