Voltage-gated Ca2+ channel mRNAs and T-type Ca2+ currents in rat gonadotropin-releasing hormone neurons

Tanaka, Nobuyuki; Ishii, Hirotaka; Yin, Chengzhu; Koyama, Mamoru; Sakuma, Yasuo; Kato, Masakatsu

doi:10.1007/s12576-010-0085-z

Cited by 13 publications

(11 citation statements)

References 31 publications

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“…Consistent with published data in rat, we found that most of the HVA channel subtypes are expressed in mouse GnRH neurons with the R-type channel expression being the most prominent (Kato et al, 2003; Tanaka et al, 2010). Moreover Ca V 1.3 (L), Ca V 2.2 (N) and Ca V 2.3 (R) mRNAs, were significantly increased in E2-treated animals.. Interestingly, the HVA L - and N-type peak currents in GnRH neurons exhibit diurnal variation in E2-treated, but not in oil-treated mice, with reduced current amplitude in the morning and increased current amplitude in the evening (Sun et al, 2010).…”

Section: Discussionsupporting

confidence: 91%

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mRNA expression of ion channels in GnRH neurons: Subtype-specific regulation by 17β-estradiol

Bosch

Tonsfeldt

Rønnekleiv

2013

Molecular and Cellular Endocrinology

114

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Burst firing of neurons optimizes neurotransmitter release. GnRH neurons exhibit burst firing activity and T-type calcium channels, which are vital for burst firing activity, are regulated by 17β-estradiol (E2) in GnRH neurons. To further elucidate ion channel expression and E2 regulation during positive and negative feedback on GnRH neurosecretion, we used single cell RT-PCR and real-time qPCR to quantify channel mRNA expression in GnRH neurons. GFP-GnRH neurons expressed numerous ion channels important for burst firing activity. E2-treatment sufficient to induce an LH surge increased mRNA expression of HCN1 channels, which underlie the pacemaker current, the calcium-permeable CaV1.3, CaV2.2, CaV2.3 channels, and TRPC4 channels, which mediate the kisspeptin excitatory response. E2 also decreased mRNA expression of SK3 channels underlying the medium AHP current. Therefore, E2 exerts fundamental changes in ion channel expression in GnRH neurons, to prime them to respond to incoming stimuli with increased excitability at the time of the surge.

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Section: Discussionsupporting

confidence: 91%

“…There are four L-type channel isoforms (Ca V 1.1, 1.2, 1.3, 1.4), but only Ca V 1.2 and Ca V 1.3 have been reported in rat GnRH neurons (Tanaka et al, 2010). We confirmed that Ca V 1.2 and Ca V 1.3, but not Ca V 1.4, were expressed in mouse GnRH neurons.…”

Section: Resultsmentioning

confidence: 99%

mRNA expression of ion channels in GnRH neurons: Subtype-specific regulation by 17β-estradiol

Bosch

Tonsfeldt

Rønnekleiv

2013

Molecular and Cellular Endocrinology

114

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“…Harvesting single-cell mRNAs using patch pipettes is a well-established way to collect mRNA for RT-PCR from neurons, including GnRH neurons in various laboratories (Pape et al, 2001; Xu et al, 2008; Zhang et al, 2009, 2015; Tanaka et al, 2010; Bhattarai et al, 2011). In our present study, the mRNA content of the individual GnRH neurons of male mice used in PCR experiments was also harvested using the patch clamp pipette, as described earlier (Farkas et al, 2013; Vastagh et al, 2015) with slight modification.…”

Section: Methodsmentioning

confidence: 99%

Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways

Farkas

Vastagh

Farkas

et al. 2016

Front. Cell. Neurosci.

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Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM–5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs) frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9–39) (1 μM). Intracellular application of the G-protein inhibitor GDP-β-S (2 mM) impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP-1 on GnRH neurons. Blockade of nitric-oxide (NO) synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 100 μM) or N5-[Imino(propylamino)methyl]-L-ornithine hydrochloride (NPLA; 1 μM) or intracellular scavenging of NO by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO; 1 mM) partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using cannabinoid receptor type-1 (CB1) inverse-agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl) pyrazole-3-carboxamide (AM251; 1 μM). Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the transient receptor potential vanilloid 1 (TRPV1)-antagonist 2E-N-(2, 3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-(1, 1-dimethylethyl)phenyl]-2-Propenamide (AMG9810; 10 μM) or the fatty acid amide hydrolase (FAAH)-inhibitor PF3845 (5 μM) impeded the GLP-1-triggered endocannabinoid pathway indicating an anandamide-TRPV1-sensitive control of 2-arachidonoylglycerol (2-AG) production. Furthermore, GLP-1 immunoreactive (IR) axons innervated GnRH neurons in the hypothalamus suggesting that GLP-1 of both peripheral and neuronal sources can modulate GnRH neurons. RT-qPCR study confirmed the expression of GLP-1R and neuronal NO synthase (nNOS) mRNAs in GnRH-GFP neurons. Immuno-electron microscopic analysis revealed the presence of nNOS protein in GnRH neurons. These results indicate that GLP-1 exerts direct facilitatory actions via GLP-1R on GnRH neurons and modulates NO and 2-AG retrograde signaling mechanisms that control the presynaptic excitatory GABAergic inputs to GnRH neurons.

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“…As found in other neuronal systems, the role of I T is to initiate transient membrane depolarizations, which recruit high voltage-activated (HVA) calcium channels to increase calcium influx [39,40]. This is of functional significance since HVA calcium currents are prevalent in GnRH neurons [41], but they can only be activated from a more depolarized state, whereas low voltage-activated T-type currents are recruited from a more hyperpolarized state (i.e., they provide the signal for setting off burst firing) [32,38,41-44]. Importantly, the T-type Ca V 3.3 channel subunit expression and current density are significantly enhanced with a high LH surge-inducing E2 treatment, facilitating the excitation of GnRH neurons [32].…”

Section: E2 Modulation Of Gnrh Neuronal Activity Through Channel Exprmentioning

confidence: 99%

Kisspeptin and Gonadotropin-Releasing Hormone Neuronal Excitability: Molecular Mechanisms Driven by 17β-Estradiol

2014

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Kisspeptin is a neuropeptide that signals via a Gαq-coupled receptor, GPR54, in gonadotropin-releasing hormone (GnRH) neurons and is essential for pubertal maturation and fertility. Kisspeptin depolarizes and excites GnRH neurons primarily through the activation of canonical transient receptor potential (TRPC) channels and the inhibition of K⁺ channels. The gonadal steroid 17β-estradiol (E₂) upregulates not only kisspeptin (Kiss1) mRNA but also increases the excitability of the rostral forebrain Kiss1 neurons. In addition, a primary postsynaptic action of E₂ on GnRH neurons is to upregulate the expression of channel transcripts that orchestrate the downstream signaling of kisspeptin in GnRH neurons. These include not only TRPC4 channels but also low-voltage-activated T-type calcium channels and high-voltage-activated L-, N- and R-type calcium channel transcripts. Moreover, E₂ has direct membrane-initiated actions to alter the excitability of GnRH neurons by enhancing ATP-sensitive potassium channel activity, which is critical for maintaining GnRH neurons in a hyperpolarized state for the recruitment of T-type calcium channels that are important for burst firing. Therefore, E₂ modulates the excitability of GnRH neurons as well as of Kiss1 neurons by altering the expression and/or function of ion channels; moreover, kisspeptin provides critical excitatory input to GnRH neurons to facilitate burst firing activity and peptide release.

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Voltage-gated Ca2+ channel mRNAs and T-type Ca2+ currents in rat gonadotropin-releasing hormone neurons

Cited by 13 publications

References 31 publications

mRNA expression of ion channels in GnRH neurons: Subtype-specific regulation by 17β-estradiol

mRNA expression of ion channels in GnRH neurons: Subtype-specific regulation by 17β-estradiol

Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways

Kisspeptin and Gonadotropin-Releasing Hormone Neuronal Excitability: Molecular Mechanisms Driven by 17β-Estradiol

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