17 beta -Estradiol inhibits high-voltage-activated calcium channel currents in rat sensory neurons via a non-genomic mechanism

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 Ca super(2+) channels and to determine its detailed mechanism in female rat DRG neurons using whole-cell patch-clamp recordings. Application of 17 beta -estradiol (1 mu M) caused a rapid inhibition on high-voltage-activated (HVA)-, but not on low-voltage-activated (LVA)- Ca super(2+) 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 17 alpha -estradiol, the stereoisomer of the endogenous 17 beta -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 17 beta -estradiol mainly targeted on both L- and N-type Ca super(2+) currents. Overnight treatment of cells with pertussis toxin profoundly reduced 17 beta -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 17 beta -estradiol did. These results suggest that 17 beta -estradiol can modulate L- and N-type HVA Ca super(2+) 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.