title: 17Beta-estradiol inhibits high-voltage-activated calcium channel currents in rat sensory neurons via a non-genomic mechanism.
abstract: There is increasing evidence that estrogen influences electrical activity of neurons via stimulation of membrane receptors. Although the presence of intracellular estrogen receptors and their responsiveness in dorsal root ganglion (DRG) primary sensory neurons were reported, rapid electrical responses of estrogen in DRG neurons have not been reported yet. Therefore the current study was initiated to examine the rapid effects of estrogen on Ca2+ channels and to determine its detailed mechanism in female rat DRG neurons using whole-cell patch-clamp recordings. Application of 17beta-estradiol (1 microM) caused a rapid inhibition on high-voltage-activated (HVA)-, but not on low-voltage-activated (LVA)-Ca2+ currents. This rapid estrogen-mediated inhibition was reproducible and dose-dependent. This effect was also sex- and stereo-specific; it was greater in cells isolated from intact female rats and was more effective than that of 17alpha-estradiol, the stereoisomer of the endogenous 17alpha-estradiol. In addition, ovariectomy reduced the inhibition significantly but this effect was restored by administration of estrogen in ovariectomized subjects. Occlusion experiments using selective blockers revealed 17beta-estradiol mainly targeted on both L- and N-type Ca2+ currents. Overnight treatment of cells with pertussis toxin profoundly reduced 17beta-estradiol-mediated inhibition of the currents. On the other hand, estradiol conjugated to bovine serum albumin (EST-BSA) produced a similar extent of inhibition as 17beta-estradiol did. These results suggest that 17beta-estradiol can modulate L- and N-type HVA Ca2+ channels in rat DRG neurons via activation of pertussis toxin-sensitive G-protein(s) and non-genomic pathways. It is likely that such effects are important in estrogen-mediated modulation of sensory functions at peripheral level.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, Seoul.
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Lee
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Chai
authors.forename: Eunhee B
authors.initials: EB
authors.lastname: Lee
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Kim
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Oh
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010566:Virulence Factors, Bordetella; D004958:Estradiol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins