title: Pregnenolone sulfate modulates glycinergic transmission in rat medullary dorsal horn neurons.
abstract: The neurosteroid pregnenolone sulfate (PS), a representative excitatory neuromodulator, has a variety of neuropharmacological actions, such as memory enhancement and convulsant effects. In this study, the effects of PS on glycinergic transmission, such as glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs), were investigated in acutely isolated medullary dorsal horn neurons by use of a conventional whole-cell patch-clamp technique. PS significantly increased the frequency but decreased the amplitude of glycinergic mIPSCs in a concentration-dependent manner. PS also accelerated the decay time constant of glycinergic mIPSCs. The PS-induced decrease in mIPSC amplitude was due to the direct postsynaptic inhibition of glycine receptors because PS inhibited the glycine-induced Cl(-) currents in a noncompetitive manner. The PS-induced increase in mIPSC frequency was not due to the activation of α7 nicotinic acetylcholine, NMDA, σ1 receptors and voltage-dependent Ca(2+) channels, which are known to be molecular targets of PS. On the other hand, the PS-induced increase in mIPSC frequency was completely attenuated either in the Ca(2+)-free external solution or in the presence of transient receptor potential (TRP) channel blockers, suggesting that PS elicits an increase in Ca(2+) concentration within glycinergic nerve terminals via the activation of putative TRP channels. The PS-mediated modulation of glycinergic synaptic transmission, such as the enhancement of presynaptic glycine release and direct inhibition of postsynaptic glycine receptors, might have a broad impact on the excitability of medullary dorsal horn neurons and therefore affect the processing of nociceptive transmission from orofacial tissues.
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors.forename: Jung-Su
authors.initials: JS
authors.lastname: Hong
authors.forename: Jin-Hwa
authors.initials: JH
authors.lastname: Cho
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Choi
authors.forename: Maan-Gee
authors.initials: MG
authors.lastname: Lee
authors.forename: Il-Sung
authors.initials: IS
authors.lastname: Jang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D005998:Glycine / Q000378:metabolism*; D018684:Glycine Agents / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D020671:Posterior Horn Cells / Q000166:cytology* / Q000187:drug effects*; D011284:Pregnenolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018684:Glycine Agents; C018370:pregnenolone sulfate; D011284:Pregnenolone; D005998:Glycine