Modulation of P2X3 receptors by Mg2+ on rat DRG neurons in culture.
On nociceptive neurons the commonest response to ATP is a rapidly desensitizing current mediated by P2X(3) receptors and believed to be involved in certain forms of pain. P2X(3) receptor recovery from desensitization is a slow process. We studied whether Mg(2+) might modulate such ATP-evoked currents on rat cultured DRG neurons, and thus account for its analgesic action in vivo. Transient increases in extracellular Mg(2+) strongly and reversibly depressed ATP currents which had not recovered from desensitization. Ca(2+)-free solution had the same action as Mg(2+). High Mg(2+) or Ca(2+)-free modulation depended on exposure length to modified divalent cation solutions, whereas it was independent from membrane potential or intracellular Ca(2+) buffering. Paired-pulse protocols showed that high Mg(2+) or Ca(2+)-free medium delayed ATP receptor recovery from desensitization, while leaving desensitization onset apparently unchanged. Tests with various concentrations of Ca(2+) and Mg(2+) showed that the depressant action by Mg(2+) was primarily due to functional antagonism of a facilitatory effect of Ca(2+) on ATP receptor function. The present results suggest that, on sensory neurons, P2X(3) receptors could be inhibited by high Mg(2+) or lack of Ca(2+), representing a negative feedback process to limit ATP-mediated nociception.
Giniatullin
Rashid
R
Biophysics Sector and Istituto Nazionale di Fisica della Materia Unit, International School for Advanced Studies (SISSA), via Beirut 4, 34014 Trieste, Italy.
Sokolova
Elena
E
Nistri
Andrea
A
D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D008274:Magnesium / Q000502:physiology*; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3
D002021:Buffers; C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium