Inhibitory effects of clonidine on GABA-activated currents in rat DRG neurons

Whole-cell patch-clamp recordings were performed on neurons from freshly isolated rat dorsal root ganglion (DRG) to investigate modulatory effects of clonidine, an α₂-adrenoceptor agonist, on GABA-activated currents. In the majority of the neurons examined (72/75), GABA (10^-6 ~ 10^-3 mol/L) induced a concentration-dependent inward current, which could be blocked by bicuculine (10^-4 ~ 10^-5 mol/L). In 51 out of 72 cells, pretreatment with different dosages of clonidine (10^-8 ~ 10^-4 mol/L) decreased the GABA (10^-4 mol/L)-activated current by 8.5%, 19.0%, 33.4%, 44.4% and 40.3%, respectively, while clonidine itself only induced a slight inward current in a few cells (12/72). The inhibitory action of clonidine blockable by yohimbine (10^-4 mol/L) was voltage-independent and did not change the membrane conductance during the activation of GABA(A) receptor. Unlike NA, (- )-isoproterenol (10^-4 ~ 10^-5 mol/L) exerted no effect on GABA-activated currents. Intracellular application of H-7 (10^-4 mol/L) via micropipette resulted in a significant blockade of clonidine inhibition (19/20) except one cell showing only a slight inhibition (11.2%). The results suggest that the inhibitory effect of clonidine on GABA-activated currents in DRG neurons might involve phosphorylation of GABA(A) receptor following activation of α₂-adrenoceptor through a mechanism of intracellular transduction.