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 II) 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-HT(2) 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 Ca(2+) chelator. These results indicate that (1). the potentiation of 5-HT on I(Gly) is mediated by 5-HT(2) receptor and through Ca(2+)-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.
Li
Hui
H
Department of Anatomy, KK Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, PR China. deptanat@fmmu.edu.cn
Kang
Jie-Fang
JF
Li
Yun-Qing
YQ
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004357:Drug Synergism; D005998:Glycine / Q000494:pharmacology* / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology* / Q000502:physiology
D011985:Receptors, Serotonin; D012701:Serotonin; D011493:Protein Kinase C; D005998:Glycine