TY - JOUR
T1 - Rapid communication
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 - Rønnekleiv, Oline K.
AU - Kelly, Martin J.
N1 - Publisher Copyright:
© 2015 by the Endocrine Society.
PY - 2015
Y1 - 2015
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.
AB - 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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U2 - 10.1210/me.2014-1392
DO - 10.1210/me.2014-1392
M3 - Article
C2 - 25734516
AN - SCOPUS:84926304643
SN - 0888-8809
VL - 29
SP - 518
EP - 527
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 4
ER -