Serotonin potentiates the response of neurons of the superficial laminae of the rat spinal dorsal horn to gamma-aminobutyric acid

Employing the Nystatin-perforated whole-cell patch-clamp recording techniqu e, the modulatory effects of serotonin (5-HT) on gamma-aminobutyric acid (G ABA)-activated whole-cell currents were investigated in neurons acutely dis sociated from the superficial laminae (laminae I and II) of the rat spinal dorsal horn. The results showed: (1) GABA acted on GABA(A) receptors and el icited inward Cl- currents (I-GABA) at a holding potential (V-H) of -40 mV; (2) 5-HT potentiated GABA-induced Cl- current without affecting the revers al potential of I-GABA and the apparent affinity of GABA to its receptor; ( 3) alpha-methyl-5-HT, a selective agonist of 5-HT2 receptor, mimicked the p otentiation effect of 5-HT on I-GABA whereas ketanserine, an antagonist of 5-HT, receptor, blocked the potentiation effect of 5-HT; (4) Chelerythrine, an inhibitor of protein kinase C, reduced the potentiation effect of 5-HT on I-GABA. The present results indicate: (1) The potentiation of 5-HT on I- GABA is mediated by 5-HT2 receptor and through a protein kinase-dependent t ransduction pathway; (2) The interactions between 5-HT and GABA might play an important role in the modulation of nociceptive information transmission at spinal cord level. (C) 2000 Elsevier Science Inc.