Rapid communication: 17 b-estradiol increases persistent Na+ current and excitability of AVPV/PeN kiss1 neurons in female mice

Chunguang Zhang, Martha A. Bosch, Jian Qiu, Oline Ronnekleiv, Martin Kelly

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17 Citations (Scopus)

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 17b-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 a-subunit transcripts, NaV1.1, NaV1.2, and NaV1.6 and b subunits, b2 andb4. Importantly, NaV1.1a and -b2 transcripts in AVPV/PeN, but not ARC, were up-regulated 2- to 3-fold by a surge-producing dose of E2, similar to the transient calcium current channel subunit Cav 3.1. The transient calcium current collaborates with INaP to generate burst firing, and selective blockade of INaPby riluzole significantly attenuated rebound burst firing and spontaneous activity. Therefore, INaP appears to play a prominent role in AVPV/ PeN Kiss1 neurons to generate spontaneous, repetitive burst firing, which is required for the high-frequency-stimulated release of kisspeptin for exciting GnRH neurons and potentially generating the GnRH surge.

Original languageEnglish (US)
Pages (from-to)518-527
Number of pages10
JournalMolecular Endocrinology
Volume29
Issue number4
DOIs
StatePublished - 2015

Fingerprint

Preoptic Area
Estradiol
Communication
Neurons
Arcuate Nucleus of Hypothalamus
Kisspeptins
Gonadotropin-Releasing Hormone
Membrane Potentials
Riluzole
Sodium Channels
Patch-Clamp Techniques
Calcium Channels
Green Fluorescent Proteins
Sodium
Calcium
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

@article{4681010810ef4b4d85b4f7ee6313d0e3,
title = "Rapid communication: 17 b-estradiol increases persistent Na+ current and excitability of AVPV/PeN kiss1 neurons in female mice",
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 17b-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 a-subunit transcripts, NaV1.1, NaV1.2, and NaV1.6 and b subunits, b2 andb4. Importantly, NaV1.1a and -b2 transcripts in AVPV/PeN, but not ARC, were up-regulated 2- to 3-fold by a surge-producing dose of E2, similar to the transient calcium current channel subunit Cav 3.1. The transient calcium current collaborates with INaP to generate burst firing, and selective blockade of INaPby riluzole significantly attenuated rebound burst firing and spontaneous activity. Therefore, INaP appears to play a prominent role in AVPV/ PeN Kiss1 neurons to generate spontaneous, repetitive burst firing, which is required for the high-frequency-stimulated release of kisspeptin for exciting GnRH neurons and potentially generating the GnRH surge.",
author = "Chunguang Zhang and Bosch, {Martha A.} and Jian Qiu and Oline Ronnekleiv and Martin Kelly",
year = "2015",
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T2 - 17 b-estradiol increases persistent Na+ current and excitability of AVPV/PeN kiss1 neurons in female mice

AU - Zhang, Chunguang

AU - Bosch, Martha A.

AU - Qiu, Jian

AU - Ronnekleiv, Oline

AU - Kelly, Martin

PY - 2015

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N2 - 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 17b-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 a-subunit transcripts, NaV1.1, NaV1.2, and NaV1.6 and b subunits, b2 andb4. Importantly, NaV1.1a and -b2 transcripts in AVPV/PeN, but not ARC, were up-regulated 2- to 3-fold by a surge-producing dose of E2, similar to the transient calcium current channel subunit Cav 3.1. The transient calcium current collaborates with INaP to generate burst firing, and selective blockade of INaPby riluzole significantly attenuated rebound burst firing and spontaneous activity. Therefore, INaP appears to play a prominent role in AVPV/ PeN Kiss1 neurons to generate spontaneous, repetitive burst firing, which is required for the high-frequency-stimulated release of kisspeptin for exciting GnRH neurons and potentially generating the GnRH surge.

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