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Volume 16, Number 11,
Issue of June 1, 1996
pp. 3620-3629
Copyright ©1996 Society for Neuroscience
17 -Estradiol Potentiates Kainate-Induced Currents via
Activation of the cAMP Cascade
Received Jan. 5, 1996; revised Feb. 27, 1996; accepted March 8, 1996.
Qin Gu and
Robert L. Moss
Department of Physiology, University of Texas Southwestern Medical
Center at Dallas, Dallas, Texas 75235
Evidence for nongenomic actions of steroids is now coming from a
variety of fields of steroid research. Mechanisms of steroid action are
being studied with regard to the membrane receptors and the activation
of second messengers. The present study investigated the mechanism for
the rapid effect of estrogen on acutely dissociated hippocampal CA1
neurons by using the whole-cell, voltage-clamp recording. Under the
perforated patch configuration, 17 -estradiol potentiated
kainate-induced currents in 38% of tested neurons. The potentiation
was stereospecific, rapid in onset, and reversible after the removal of
the steroid. Dose-response curves show that the potentiation by
17 -estradiol was evident at a concentration as low as 10 nM and saturated at 10 µM. 17 -Estradiol did not affect the kinetics
(i.e., affinity and cooperativity) and reversal potential of
kainate-induced currents. This suggests that the potentiation did not
result from direct interaction with kainate receptors nor the
activation of ion channels other than kainate receptor-channels. The
potentiation by 17 -estradiol was similar to the enhancement of
kainate-induced currents evoked by 8-bromo-cAMP, and was modulated by
an inhibitor of phosphodiesterase (IBMX). The estrogen potentiation was
blocked by a specific blocker of PKA (Rp-cAMPS). Under
standard recording configuration, the effect was significantly affected
by intracellular perfusing with GDP- -S or GTP- -S. The data
suggest that the potentiation of kainate-induced currents by
17 -estradiol was likely a G-protein(s) coupled, cAMP-dependent
phosphorylation event. By involvement of this nongenomic mechanism,
estrogen may play a role in the modulation of excitatory synaptic
transmission in the hippocampus.
Key words:
steroid hormone;
modulator;
non-NMDA receptor;
inward current;
PKA;
G-protein;
nongenomic
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