Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord.
Using spinal cord slice preparations and patch-clamp recordings in lamina II and lamina V regions, we tested a hypothesis that P2X receptor subtypes differentially modulate glutamate release from primary afferent terminals innervating different sensory regions. We found that activation of P2X receptors by alpha,beta-methylene-ATP increased glutamate release onto >80% of DH neurons in both lamina regions. However, two distinct types of modulation, a transient and a long-lasting enhancement of glutamate release were observed. In lamina II recordings, >70% of the modulation was transient. In contrast, P2X receptor-mediated modulation was always long-lasting in lamina V. Pharmacologically, both transient and long-lasting types of modulation were blocked by 10 microM pyridxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium, a broad-spectrum P2X receptor antagonist. Transient modulation was not observed in the presence of 1 microM trinitrophenyl-ATP (TNP-ATP), a subtype-selective P2X receptor antagonist, suggesting that homomeric P2X3 receptors may be involved in the transient modulation in lamina II. The long-lasting modulation remained in the presence of 1 microM TNP-ATP. Selective removal of P2X3-expressing afferent terminals by the targeting toxin saporin-conjugated isolectin B4 or surgical removal of superficial DH did not affect P2X receptor-mediated long-lasting modulation in lamina V. Taken together, these results suggest that P2X receptor subtypes play distinct roles in sensory processing in functionally different sensory regions.
Nakatsuka
Terumasa
T
McKnight Brain Institute and Department of Oral Surgery, Division of Neuroscience, College of Dentistry, University of Florida, Gainesville, Florida, 32610, USA.
Tsuzuki
Kenzo
K
Ling
Jennifer X
JX
Sonobe
Hideki
H
Gu
Jianguo G
JG
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission
C546410:P2rx3 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D018698:Glutamic Acid; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate