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

1. The modulation by adenosine of GABA-activated current (I-GABA) 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 mu M) suppressed I-GABA, while in some neurons examined, it potentiated (16/90, 17.8%) I-GABA. It exerted no effects on I-GABA 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 I-GABA showed no voltage dependence. 4. 8-Cyclopentyl-1,3-dimethylxanthine (DPCPX; 1 mu M), a selective A(1) adenosine receptor antagonist, partially reversed adenosine inhibition of I-GABA and completely blocked N-6-cyclohexyladenosine (CHA; an A(1) adenosine receptor agonist) inhibition of I-GABA. DPCPX (1 mu M) also blocked the suppression of I-GABA by 2-chloroadenosine (CADO). CGS 21680, a selective A(2A) adenosine receptor agonist, did not inhibit I-GABA, and DMPX, a selective A(2A) adenosine receptor antagonist, did not prevent adenosine inhibition of I-GABA. 5. Intracellular application of H-7 (20 mu M; a protein kinase C inhibitor) reversed adenosine inhibition of I-GABA while inclusion of cAMP (1 mM), H-9 (20 mu M; a protein kinase A inhibitor) and BAPTA (10 mM; a chelator of calcium ions) in the recording pipette did not affect the depression of I-GABA by adenosine. I-GABA 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.