Adenosine suppresses GABA A receptor-mediated responses in rat sacral dorsal commissural neurons

Abstract

The modulatory effect of adenosine on γ-aminobutyric acid (GABA)-activated whole-cell currents were investigated in the neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin perforated patch recording configuration under the voltage-clamp conditions. The results showed that: (1) GABA acted on GABA A receptor and elicited inward Cl − currents ( I GABA) at a holding potential ( V H) of −40 mV; (2) adenosine suppressed GABA-induced Cl − current without affecting the reversal potential of I GABA and the apparent affinity of GABA to its receptor; (3) N6-cyclohexyladenosine mimicked the suppression effect of adenosine on I GABA, whereas 8-cyclopentyl-1,3-dipropylxanthine blocked the suppression effect of adenosine; (4) adenosine fails to suppress I GABA on the neurons that were pretreated with bisindolylmaleimide I (BIM), while after pretreatment with H-89, the inhibitory effect of adenosine on I GABA were not affected; (5) the suppression effect of adenosine on I GABA remained in the presence of BAPTA-AM. The present results indicate that the suppression of adenosine on I GABA is mediated by adenosine A 1 receptor and through a Ca 2+-independent protein kinase C transduction pathway, and that the interactions between adenosine and GABA might participate in the modulation of nociceptive information transmission at the SDCN.