Molecular characterization of T-type Ca2+ channels responsible for low threshold spikes in hypothalamic paraventricular nucleus neurons

Lee, S.; Han, Tae Hee; Sonner, Patrick M.; Stern, Javier E.; Ryu, Pan Dong; Lee, S.Y.

doi:10.1016/j.neuroscience.2008.06.055

Cited by 21 publications

(39 citation statements)

References 43 publications

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“…However, based on the number of neurons that we were able to detect, it appears that Cav3.3 and Cav3.2 are the most abundant in GnRH neurons, whereas the mRNA expression of Cav3.1 is less plentiful. This is different from most other hypothalamic neurons (areas) where Cav3.1 is more highly expressed (Lee et al, 2008; Bosch et al, 2009). The relatively slow inactivation of the T-type current in GnRH neurons is consistent with channels composed of Cav3.3 (α 1 I) subunits (Klockner et al, 1999; Monteil et al, 2000; Chemin et al, 2002; Perez-Reyes, 2003; Park et al, 2004).…”

Section: Discussioncontrasting

confidence: 76%

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17β-Estradiol Regulation of T-Type Calcium Channels in Gonadotropin-Releasing Hormone Neurons

Zhang¹,

Bosch²,

Rick³

et al. 2009

J. Neurosci.

120

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T-type calcium channels are responsible for generating low-threshold spikes that facilitate burst firing and neurotransmitter release in neurons. Gonadotropin-releasing hormone (GnRH) neurons exhibit burst firing, but the underlying conductances are not known. Previously, we found that 17␤-estradiol (E2) increases T-type channel expression and excitability of hypothalamic arcuate nucleus neurons. Therefore, we used ovariectomized oil-or E2-treated EGFP (enhanced green fluorescent protein)-GnRH mice to explore the expression and E2 regulation of T-type channels in GnRH neurons. Based on single-cell reverse transcriptase-PCR and real-time PCR quantification of the T-type channel ␣ 1 subunits, we found that all three subunits were expressed in GnRH neurons, with expression levels as follows: Cav3.3 Ն Cav3.2 Ͼ Cav3.1. The mRNA expression of the three subunits was increased with surge-inducing levels of E2 during the morning. During the afternoon, Cav3.3 mRNA expression remained elevated, whereas Cav3.1 and Cav3.2 were decreased. The membrane estrogen receptor agonist STX increased the expression of Cav3.3 but not Cav3.2 in GnRH neurons. Whole-cell patch recordings in GnRH neurons revealed that E2 treatment significantly augmented T-type current density at both time points and increased the rebound excitation during the afternoon. Although E2 regulated the mRNA expression of all three subunits in GnRH neurons, the increased expression combined with the slower inactivation kinetics of the T-type current indicates that Cav3.3 may be the most important for bursting activity associated with the GnRH/LH (luteinizing hormone) surge. The E2-induced increase in mRNA expression, which depends in part on membrane-initiated signaling, leads to increased channel function and neuronal excitability and could be a mechanism by which E2 facilitates burst firing and cyclic GnRH neurosecretion.

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Section: Discussioncontrasting

confidence: 76%

“…All three subunits are expressed in the preoptic and basal hypothalamic regions (Qiu et al, 2006a; Bosch et al, 2009). However in the hypothalamic paraventricular (PVH) nucleus, Cav3.1 is the major subtype that mediates T-type calcium channel-dependent low threshold spikes (LTS) (Lee et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

17β-Estradiol Regulation of T-Type Calcium Channels in Gonadotropin-Releasing Hormone Neurons

Zhang¹,

Bosch²,

Rick³

et al. 2009

J. Neurosci.

120

View full text Add to dashboard Cite

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“…To further prove the expression of functional corticosteroid receptors, we examined the effects of the activation of corticosteroid receptors on the firing properties of GABAergic neurons in AHA. We compared the burst firing [23][24][25] induced by injecting 20∼60 pA of depolarizing current pulses (500-ms) from a holding potential of −75 mV to −85 mV [21,22]. Burst firing appeared in the cluster of spikes riding on a slow depolarization, as reported by Okuhara and Beck (1998).…”

Section: Effects Of Corticosteroid Receptor Activation On Burst Firinmentioning

confidence: 87%

Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior Hypothalamic Area of GAD65-eGFP Mice

Shin¹,

Han²,

Lee³

et al. 2011

Korean J Physiol Pharmacol

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Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11∼ 14% , p＜ 0.01 by χ 2 -test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.

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“…However, the neuronal properties of PVN-RVLM neurons are determined not only by I A , but also by a variety of other factors. Regarding the intrinsic membrane property, other ionic currents besides I A , including voltage-gated calcium channels and small conductance calcium-activated potassium channels, participate in determining the excitability of PVN-RVLM neurons [15,40]. Studies have reported that E2 modulates these channels in other neuronal cells within the brain [41-43].…”

Section: Discussionmentioning

confidence: 99%

Estrogen replacement modulates voltage-gated potassium channels in rat presympathetic paraventricular nucleus neurons

2013

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BackgroundThe hypothalamic paraventricular nucleus (PVN) is an important site in the regulation of the autonomic nervous system. Specifically, PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) play a regulatory role in the determination of the sympathetic outflow in the cardiovascular system. In the PVN-RVLM neurons, the estrogen receptor β is expressed. However, to date, the effects of estrogen on PVN-RVLM neurons have not been reported. The present study investigated estrogen-mediated modulation of two voltage-gated potassium channel (Kv) subunits, Kv4.2 and Kv4.3, that are expressed predominantly in PVN neurons and the functional current of Kv4.2 and Kv4.3, the transient outward potassium current (IA).ResultsSingle-cell real-time RT-PCR analysis showed that 17β-estradiol (E2) replacement (once daily for 4 days) selectively down-regulated Kv4.2 mRNA levels in the PVN-RVLM neurons of ovariectomized female rats. There was no change in Kv4.3 levels. Whole-cell patch-clamp recordings demonstrated that E2 also diminished IA densities. Interestingly, these effects were most apparent in the dorsal cap parvocellular subdivision of the PVN. E2 also shortened a delay in the excitation of the PVN-RVLM neurons.ConclusionsThese findings demonstrate that E2 exerts an inhibitory effect on the functions of IA, potentially by selectively down-regulating Kv4.2 but not Kv4.3 in PVN-RVLM neurons distributed in a specific parvocellular subdivision.

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Molecular characterization of T-type Ca2+ channels responsible for low threshold spikes in hypothalamic paraventricular nucleus neurons

Cited by 21 publications

References 43 publications

17β-Estradiol Regulation of T-Type Calcium Channels in Gonadotropin-Releasing Hormone Neurons

17β-Estradiol Regulation of T-Type Calcium Channels in Gonadotropin-Releasing Hormone Neurons

Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior Hypothalamic Area of GAD65-eGFP Mice

Estrogen replacement modulates voltage-gated potassium channels in rat presympathetic paraventricular nucleus neurons

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