期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 4, 页码 797-807出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4019-03.2004
关键词
ATP; P2Y receptor; calcium channel; dorsal root ganglion; patch clamp; analgesia
Patch-clamp recordings from small-diameter rat dorsal root ganglion (DRG) neurons maintained in culture demonstrated preferential inhibition by ATP of high-voltage-activated, but not low-voltage-activated, Ca2+ currents (I-Ca). The rank order of agonist potency was UTP > ADP > ATP. ATP depressed the omega-conotoxin GVIA-sensitive N-type current only. Pyridoxal-5-phosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS) and 2'-deoxy-N-6-methyladenosine 3', 5'-bisphosphate tetraammonium, two P2Y(1) receptor antagonists, almost abolished the ATP-induced inhibition. Both patch-clamp recordings and immunocytochemistry coupled with confocal laser microscopy indicated a colocalization of functional P2X(3) and P2Y(1) receptors on the same DRG neurons. Because the effect of ATP was inhibited by intracellular guanosine 5'-O-(2-thiodiphosphate) or by applying a strongly depolarizing prepulse, P2Y(1) receptors appear to block I-Ca by a pathway involving the betagamma subunit of a G(q/11) protein. Less efficient buffering of the intracellular Ca2+ concentration ([Ca2+](i)) by reducing the intrapipette EGTA failed to interfere with the ATP effect. Fura-2 microfluorimetry suggested that ATP raised [Ca2+](i) by a Galpha-mediated release from intracellular pools and simultaneously depressed the high external potassium concentration-induced increase of [Ca2+](i) by inhibiting I-Ca via Gbetagamma. Adenosine 5'-O-(2-thiodiphosphate) inhibited dorsal root-evoked polysynaptic population EPSPs in the hemisected rat spinal cord and prolonged the nociceptive threshold on intrathecal application in the tail-flick assay. These effects were not antagonized by PPADS. Hence, P2Y receptor activation by ADP, which is generated by enzymatic degradation of ATP, may decrease the release of glutamate from DRG terminals in the spinal cord and thereby partly counterbalance the algogenic effect of ATP.
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