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Presynaptic modulation of synaptic transmission by pregnenolone sulfate as studied by optical recordings.
J Neurophysiol 2005; 94(6):4131-44JN

Abstract

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.

Authors+Show Affiliations

International Cooperative Research Project/Solution Oriented Research for Science and Technology Cell Mechanosensing, Japan Science and Technology Agency, Nagoya.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15972828

Citation

Chen, Ling, and Masahiro Sokabe. "Presynaptic Modulation of Synaptic Transmission By Pregnenolone Sulfate as Studied By Optical Recordings." Journal of Neurophysiology, vol. 94, no. 6, 2005, pp. 4131-44.
Chen L, Sokabe M. Presynaptic modulation of synaptic transmission by pregnenolone sulfate as studied by optical recordings. J Neurophysiol. 2005;94(6):4131-44.
Chen, L., & Sokabe, M. (2005). Presynaptic modulation of synaptic transmission by pregnenolone sulfate as studied by optical recordings. Journal of Neurophysiology, 94(6), pp. 4131-44.
Chen L, Sokabe M. Presynaptic Modulation of Synaptic Transmission By Pregnenolone Sulfate as Studied By Optical Recordings. J Neurophysiol. 2005;94(6):4131-44. PubMed PMID: 15972828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Presynaptic modulation of synaptic transmission by pregnenolone sulfate as studied by optical recordings. AU - Chen,Ling, AU - Sokabe,Masahiro, Y1 - 2005/06/22/ PY - 2005/6/24/pubmed PY - 2006/1/26/medline PY - 2005/6/24/entrez SP - 4131 EP - 44 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 94 IS - 6 N2 - 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. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/15972828/Presynaptic_modulation_of_synaptic_transmission_by_pregnenolone_sulfate_as_studied_by_optical_recordings_ L2 - http://www.physiology.org/doi/full/10.1152/jn.00755.2004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -