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

1997; Wiley; Volume: 501; Issue: 1 Linguagem: Inglês

10.1111/j.1469-7793.1997.067bo.x

1469-7793

Hongzhen Hu, Zhi‐Wang Li,

Adenosine and Purinergic Signaling

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. In most of the DRG neurons examined (68/90, 75.5%) adenosine (1–100 μ 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%). Adenosine shifted the GABA concentration–response curve downward with no significant change of the EC 50 . The maximal response to GABA was suppressed by 29.6 ± 2.6%. The adenosine‐induced inhibition of I gaba showed no voltage dependence. 8‐Cyclopentyl‐1,3‐dimethylxanthine (DPCPX; 1 μ m ), a selective A 1 adenosine receptor antagonist, partially reversed adenosine inhibition of I gaba and completely blocked N 6 ‐cyclo‐hexyladenosine (CHA; an A 1 adenosine receptor agonist) inhibition of I GABA . DPCPX (1 μ 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 . Intracellular application of H‐7 (20 μ m ; a protein kinase C inhibitor) reversed adenosine inhibition of I gaba while inclusion of cAMP (1 m m ), H‐9 (20 μ m ; a protein kinase A inhibitor) and BAPTA (10 m m ; 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. The results suggest that adenosine, as a neuromodulator, exerts a modulatory effect on the GABA‐induced presynaptic inhibition in primary sensory transmission.