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Convergent control of synaptic GABA release from rat dorsal horn neurones by adenosine and GABA autoreceptors
Author(s) -
Hugel Sylvain,
Schlichter Rémy
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 - 10.1113/jphysiol.2003.047894
Subject(s) - gabab receptor , autoreceptor , gabaergic , neuroscience , inhibitory postsynaptic potential , adenosine , postsynaptic potential , chemistry , biology , gabaa receptor , receptor , agonist , biochemistry
Perforated patch clamp recordings were performed on cultured superficial neonatal rat dorsal horn (DH) spinal cord neurones in order to study the presynaptic modulation of GABA release at unitary synaptic connections. Since ATP can be coreleased with GABA at about two‐thirds of GABAergic synapses between DH neurones, and can be rapidly metabolized to adenosine in the extracellular space, we investigated the potential role of A1 adenosine receptors and GABA B receptors which might function as inhibitory autoreceptors. Adenosine and GABA B receptor agonists reduced the amplitude of electrically evoked GABAergic inhibitory postsynaptic currents (eIPSCs) as well as the frequency of GABAergic miniature IPSCs, suggesting a presynaptic action of these substances. The actions of adenosine were blocked by the A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX). The effects of adenosine and GABA B agonists were occlusive, indicating a functional convergence of the signalling pathways engaged by A1 and GABA B receptors. A1 and GABA B antagonists increased the amplitude of eIPSCs in a supra‐additive manner, suggesting a tonic activation of these receptors by ambient adenosine and GABA. Moreover, using trains of electrical stimulations, we were able to unravel a phasic (activity‐dependent) activation of presynaptic A1 and GABA B autoreceptors only in the case of neurones coreleasing ATP and GABA, despite the presence of functional presynaptic A1 and GABA B receptors on all GABAergic DH neurones. This selective, convergent and activity‐dependent inhibition of GABA release by A1 and GABA B autoreceptors might modulate the integrative properties of postsynaptic DH neurones under physiological conditions and/or during the development of pathological pain states.