Presynaptic modulation of synaptic transmission by pregnenolone sulfate as studied by optical recordings.
The effects of pregnenolone sulfate (PREGS), a putative neurosteroid, on the transmission of perforant path-granule cell synapses were investigated with an optical recording technique in rat hippocampal slices stained with voltage-sensitive dyes. Application of PREGS to the bath solution resulted in an acute augmentation of EPSP in a dose-dependent manner. The PREGS effect was dependent on the extracellular Ca(2+) concentration ([Ca(2+)](o)), but independent of NMDA receptor activation. PREGS caused a decrease in paired-pulse facilitation, which implies that PREGS positively modulates presynaptic neurotransmitter releases. Firmer support for this mechanism was that PREGS augmented the synaptically induced glial depolarization (SIGD) that reflects the activity of electrogenic glutamate transporters in glial cells during the uptake of released glutamate. The selective alpha7nAChR antagonist alpha-BGT or MLA prevented the SIGD increase by PREGS. Furthermore DMXB, a selective alpha7nAChR agonist, mimicked the PREGS effect on SIGD and antagonized the effect of PREGS. The presynaptic effect of PREGS was partially attenuated by the L-type Ca(2+) channel (VGCC) blocker nifedipine. Based on these findings, we proposed a novel mechanism underlying the facilitated synaptic transmission by PREGS: this neurosteroid sensitizes presynaptic alpha7nAChR that is followed by an activation of L-type VGCC to increase the presynaptic glutamate release.
International Cooperative Research Project/Solution Oriented Research for Science and Technology Cell Mechanosensing, Japan Science and Technology Agency, Nagoya.
Ling
L
Chen
Masahiro
M
Sokabe
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005029:Ethylenediamines / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D001597:Benzylidene Compounds; D002038:Bungarotoxins; D002121:Calcium Channel Blockers; D018492:Dopamine Antagonists; D005029:Ethylenediamines; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; C018370:pregnenolone sulfate; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; C054634:methyllycaconitine; D013779:Tetrodotoxin; C020889:dihydrokainic acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D011284:Pregnenolone; D015763:2-Amino-5-phosphonovalerate; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D006220:Haloperidol; D007608:Kainic Acid; D002118:Calcium; D000157:Aconitine; D001640:Bicuculline