Serotonin potentiation of glycine-activated whole-cell currents in the superficial laminae neurons of the rat spinal dorsal horn is mediated by protein kinase C

The modulatory effects of serotonin (5-HT) on glycine (Gly)-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae (I and 11) of the rat spinal dorsal horn using the nystatin-perforated patch recording configuration under voltage-clamp conditions. Our results demonstrate that (1) Gly acted on strychnine (STR)-sensitive Gly receptors and elicited inward Cl- currents (I-Gly) at a holding potential of -40 mV; (2) 5-HT potentiated I-Gly without affecting the reversal potential of I-Gly; (3) the agonist (alpha-methyl-5-HT) and antagonist (ketanserine) of 5-HT2 receptor mimicked and blocked the potentiating effect of 5-HT on I-Gly, respectively; (4) bisindolylmaleimide I (BIM), a selective inhibitor of protein kinase C (PKC), reduced the potentiating effect of 5-HT on I-Gly; and (5) 5-HT-induced enhancement of I-Gly was not affected by pretreatment with 1,2-bis-(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxy-methyl) ester (BAPTA AM), a Ca2+ chelator. These results indicate that (1) the potentiation of 5-HT on I-Gly is mediated by 5-HT2 receptor and through Ca2+-independent PKC intracellular signal transduction pathway; and (2) the interactions between 5-HT and Gly might modulate the transmission of nociceptive information through the spinal cord. (C) 2002 Elsevier Science Inc. All rights reserved.