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 non-nociceptive stimuli. In the present study, effects of ATP were studied on axons and Schwann cells of C fibres in isolated rat vagus nerves. A combination of a computerised threshold tracking technique with photometric and confocal measurements of the free intracellular Ca2+ concentration revealed differences in the effect of ATP and related compounds. Pyridoxal-phosphate-6-azophenyl-2',5'-disulphonic acid (iso-PPADS, an antagonist of ionotropic P2X receptors) completely blocked the excitatory effect of alpha,beta-meATP on unmyelinated 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 confocal imaging experiments, the lectin IB4 was used to identify unmyelinated 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 during a rise in [Ca2+]i induced by inhibition of the endoplasmic Ca2 ATPase with cyclopiazonic acid. These data show that an increase of the extracellular ATP concentration in an intact peripheral nerve trunk activates both axons and Schwann cells. It appears that P2 nucleotide receptors on Schwann cells may contribute to the excitatory effect of ATP observed on unmyelinated, including nociceptive, axons.
Irnich
Dominik
D
Department of Anesthesiology, University of Munich, Marchioninistr. 15, D-81377 Munich, Germany Department of Physiology, University of Munich, D-80336 Munich, Germany Sobell Department of Neurophysiology, Institute of Neurology, London WC1N 3BG, UK.
Burgstahler
Ralf
R
Bostock
Hugh
H
Grafe
Peter
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D010975:Platelet Aggregation Inhibitors; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C006979:2-chloro-ATP; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium