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-regulated 2- to 3-fold by a surge-producing dose of E2, similar to the transient
calcium current channel subunit Cav3.1. The transient
calcium current collaborates with
INaP to generate burst firing, and selective blockade of
INaP by
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.