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Control of glutamatergic neurotransmission in the rat spinal dorsal horn by the nucleoside transporter ENT1
Author(s) -
Ackley Michael A.,
Governo Ricardo J. M.,
Cass Carol E.,
Young James D.,
Baldwin Stephen A.,
King Anne E.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00507.x
Subject(s) - adenosine , neurotransmission , excitatory postsynaptic potential , glutamatergic , adenosine deaminase , nucleoside transporter , chemistry , adenosine a1 receptor , nucleoside , adenosine receptor , neuroscience , patch clamp , glutamate receptor , agonist , pharmacology , biology , inhibitory postsynaptic potential , biochemistry , receptor , transporter , gene
Adenosine modulates nociceptive processing in the superficial dorsal horn of the spinal cord. In other tissues, membrane transporters influence profoundly the extracellular levels of adenosine. To investigate the putative role of nucleoside transporters in the regulation of excitatory synaptic transmission in the dorsal horn, we employed immunohistochemistry and whole‐cell patch‐clamp recording of substantia gelatinosa neurons in slices of rat spinal cord in vitro . The rat equilibrative nucleoside transporter (rENT1) was revealed by antibody staining to be abundant in neonatal and mature dorsal horn, especially within laminae I‐III. This was confirmed by immunoblots of dorsal horn homogenate. Nitrobenzylthioinosine (NBMPR), a potent non‐transportable inhibitor of rENT1, attenuated synaptically evoked EPSCs onto lamina II neurons in a concentration‐dependent manner. Application of an adenosine A1 antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine produced a parallel rightward shift in the NBMPR concentration‐effect curve. The effects of NBMPR were partially reversed by adenosine deaminase, which facilitates the metabolic degradation of adenosine. The modulation by NBMPR of evoked EPSCs was mimicked by exogenous adenosine or the selective A1 receptor agonist, 2‐chloro‐ N 6 ‐cyclopentyl adenosine. NBMPR reduced the frequency but not the amplitude of spontaneous miniature EPSCs and increased the paired‐pulse ratio of evoked currents, an effect that is consistent with presynaptic modulation. These data provide the first direct evidence that nucleoside transporters are able to critically modulate glutamatergic synaptic transmission.