17β-Estradiol increases persistent Na(+) current and excitability of AVPV/PeN Kiss1 neurons in female mice

Molecular Endocrinology
Chunguang ZhangMartin J Kelly

Abstract

In vitro slice studies have revealed that there are significant differences in the spontaneous firing activity between anteroventral periventricular/periventricular preoptic nucleus (AVPV/PeN) and arcuate nucleus (ARC) kisspeptin (Kiss1) neurons in females. Although both populations express similar endogenous conductances, we have discovered that AVPV/PeN Kiss1 neurons express a subthreshold, persistent sodium current (INaP) that dramatically alters their firing activity. Based on whole-cell recording of Kiss1-Cre-green fluorescent protein (GFP) neurons, INaP was 4-fold greater in AVPV/PeN vs ARC Kiss1 neurons. An LH surge-producing dose of 17β-estradiol (E2) that increased Kiss1 mRNA expression in the AVPV/PeN, also augmented INaP in AVPV/PeN neurons by 2-fold. Because the activation threshold for INaP was close to the resting membrane potential (RMP) of AVPV/PeN Kiss1 neurons (-54 mV), it rendered them much more excitable and spontaneously active vs ARC Kiss1 neurons (RMP = -66 mV). Single-cell RT-PCR revealed that AVPV/PeN Kiss1 neurons expressed the requisite sodium channel α-subunit transcripts, NaV1.1, NaV1.2, and NaV1.6 and β subunits, β2 and β4. Importantly, NaV1.1α and -β2 transcripts in AVPV/PeN, but not ARC, were up-...Continue Reading

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Citations

Apr 11, 2017·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Miro KasumEmina Ejubović
May 20, 2020·Nature Reviews. Endocrinology·Víctor M Navarro
Jul 21, 2017·Frontiers in Cellular Neuroscience·Csaba Vastagh, Zsolt Liposits
Jun 24, 2019·Steroids·Todd L StincicMartin J Kelly

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