Voltage-Gated Potassium Currents Are Targets of Diurnal Changes in Estradiol Feedback Regulation and Kisspeptin Action on Gonadotropin-Releasing Hormone Neurons in Mice

Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, USA.
Biology of Reproduction (Impact Factor: 3.32). 07/2011; 85(5):987-95. DOI: 10.1095/biolreprod.111.093492
Source: PubMed


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, I(A), and a sustained current, I(K). 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 I(A) or I(K) in GnRH neurons from OVX mice. In contrast, in GnRH neurons from OVX+E mice, I(A) and I(K) were greater during the morning when GnRH neuron activity is low and smaller in the evening when GnRH neuron activity is high. Estradiol increased I(A) in the morning and decreased it in the evening, relative to that in cells from OVX mice. Exogenously applied kisspeptin reduced I(A) regardless of time of day or estradiol status. Estradiol, interacting with time of day, and kisspeptin both depolarized I(A) 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.

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Available from: Justyna Pielecka-Fortuna, Sep 10, 2014
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    • "I K Yes Yes Herbison, 1998; 25 Pielecka-Fortuna et al., 2011 26 I M No No Xu et al., 2008 21 S K Yes No Bosch et al., 2003; 24 Kelly et al., 2002; 22 Kelly et al., 2003; 23 Kato et al., 2006; 29 Liu and Herbison, 2008; 13 Lee et al., 2010 30 B K No No Hiraizumi et al., 2008 31 KATP Yes No Zhang et al., 2007 27 Calcium L-type Yes Yes Nunemaker et al., 2003; 33 Sun et al., 2010 N-type Yes Yes Nunemaker et al., 2003; 33 Sun et al., 2010 P-type No No Nunemaker et al., 2003 33 Q-type No No Nunemaker et al., 2003 33 R-type Yes Yes Nunemaker et al., 2003; 33 Sun et al., 2010 T-type Yes No Kato et al., 2003; 34 Nunemaker et al., 2003; 33 Zhang et al., 2009 36 Chloride GABA A No No Weyler et al., 1999; Herbison and Moenter, 2011 38 Summary table of the ionic conductances described for GnRH neurons. Intrinsic GnRH conductances, estrogen sensitivity, and diurnal effects are listed per conductance type. "
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