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20 July 2011 Voltage-Gated Potassium Currents Are Targets of Diurnal Changes in Estradiol Feedback Regulation and Kisspeptin Action on Gonadotropin-Releasing Hormone Neurons in Mice
Justyna Pielecka-Fortuna, R. Anthony DeFazio, Suzanne M. Moenter
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Abstract

Estradiol has both negative and positive feedback actions upon gonadotropin-releasing hormone (GnRH) release; the latter actions trigger the preovulatory GnRH surge. Although neurobiological mechanisms of the transitions between feedback modes are becoming better understood, the roles of voltage-gated potassium currents, major contributors to neuronal excitability, are unknown. Estradiol alters two components of potassium currents in these cells: a transient current, IA, and a sustained current, IK. Kisspeptin is a potential mediator between estradiol and GnRH neurons and can act directly on GnRH neurons. We examined how estradiol, time of day, and kisspeptin interact to regulate these conductances in a mouse model exhibiting daily switches between estradiol negative (morning) and positive feedback (evening). Whole-cell voltage clamp recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice and from OVX mice treated with estradiol (OVX E). There were no diurnal changes in either IA or IK in GnRH neurons from OVX mice. In contrast, in GnRH neurons from OVX E mice, IA and IK were greater during the morning when GnRH neuron activity is low and smaller in the evening when GnRH neuron activity is high. Estradiol increased IA in the morning and decreased it in the evening, relative to that in cells from OVX mice. Exogenously applied kisspeptin reduced IA regardless of time of day or estradiol status. Estradiol, interacting with time of day, and kisspeptin both depolarized IA activation. These findings extend our understanding of both the neurobiological mechanisms of estradiol negative vs. positive regulation of GnRH neurons and of kisspeptin action on these cells.

Justyna Pielecka-Fortuna, R. Anthony DeFazio, and Suzanne M. Moenter "Voltage-Gated Potassium Currents Are Targets of Diurnal Changes in Estradiol Feedback Regulation and Kisspeptin Action on Gonadotropin-Releasing Hormone Neurons in Mice," Biology of Reproduction 85(5), 987-995, (20 July 2011). https://doi.org/10.1095/biolreprod.111.093492
Received: 25 May 2011; Accepted: 1 July 2011; Published: 20 July 2011
JOURNAL ARTICLE
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KEYWORDS
diurnal
estradiol
estradiol receptor
feedback
GnRH receptor
gonadotropin-releasing hormone
ion channels
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