Modulation by adenosine of GABA‐activated current in rat dorsal root ganglion neurons

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Abstract
1 The modulation by adenosine of GABA‐activated current (IGABA) was studied in freshly isolated rat dorsal root ganglion (DRG) neurons using the whole‐cell patch‐clamp technique. 2 In most of the DRG neurons examined (68/90, 75.5%) adenosine (1–100 μm) suppressed Igaba, while in some neurons examined, it potentiated (16/90, 17.8%) Igaba. It exerted no effects on Igaba in a few cells (6/90, 6.7%). 3 Adenosine shifted the GABA concentration–response curve downward with no significant change of the EC50. The maximal response to GABA was suppressed by 29.6 ± 2.6%. The adenosine‐induced inhibition of Igaba showed no voltage dependence. 4 8‐Cyclopentyl‐1,3‐dimethylxanthine (DPCPX; 1 μm), a selective A1 adenosine receptor antagonist, partially reversed adenosine inhibition of Igaba and completely blocked N6‐cyclo‐hexyladenosine (CHA; an A1 adenosine receptor agonist) inhibition of IGABA. DPCPX (1 μm) also blocked the suppression of Igaba by 2‐chloroadenosine (CADO). CGS 21680, a selective A2A adenosine receptor agonist, did not inhibit Igaba and DMPX, a selective A2A adenosine receptor antagonist, did not prevent adenosine inhibition of Igaba. 5 Intracellular application of H‐7 (20 μm; a protein kinase C inhibitor) reversed adenosine inhibition of Igaba while inclusion of cAMP (1 mm), H‐9 (20 μm; a protein kinase A inhibitor) and BAPTA (10 mm; a chelator of calcium ions) in the recording pipette did not affect the depression of Igaba by adenosine. Igaba was also suppressed by internal perfusion of PMA, a protein kinase C activator. 6 The results suggest that adenosine, as a neuromodulator, exerts a modulatory effect on the GABA‐induced presynaptic inhibition in primary sensory transmission.