Molecular mechanisms that drive estradiol-dependent burst firing of Kiss1 neurons in the rostral periventricular preoptic area.
Molecular mechanisms that drive estradiol-dependent burst firing of Kiss1 neurons in the rostral periventricular preoptic area.
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DOI：
10.1152/ajpendo.00406.2013
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发表时间：
2013-12
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通讯作者：
Chunguang Zhang;K. Tonsfeldt;J. Qiu;M. Bosch;Kazuto Kobayashi;R. Steiner;M. Kelly;O. Rønnekleiv
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文献类型：
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作者：
Chunguang Zhang;K. Tonsfeldt;J. Qiu;M. Bosch;Kazuto Kobayashi;R. Steiner;M. Kelly;O. Rønnekleiv
Kissspeptin（Kiss 1）神经元位于第三脑室头侧脑室周围区（RP 3V），为促性腺激素释放激素（GnRH）神经元提供兴奋性驱动，从而控制生育。使用全细胞膜片钳记录和单细胞（sc）RT-PCR技术靶向Kiss 1-CreGFP或酪氨酸羟化酶（TH）-EGFP神经元，我们表征了这些神经元的生物物理特性，并确定了17β-雌二醇（E2）治疗的卵巢切除雌性小鼠爆发性放电所需的关键内在特性。四分之一的RP 3V Kiss 1神经元表现出自发爆发放电。RP 3V Kiss 1神经元表达超极化激活的h电流（Ih）和T型钙电流（IT），支持超极化诱导的反弹爆发放电。在电压钳条件下，所有Kiss 1神经元表达的动力学快速Ih增强3.4倍高（LH浪涌生产）-E2治疗。对Kiss 1神经元的scPCR分析揭示了HCN 1通道转录物的丰富表达。Kiss 1神经元还表达Ni（2+）和TTA-P2敏感的IT，其在高E2处理下增加6倍。CaV 3.1 mRNA在这些细胞中也有高表达。电流钳分析显示，在高E2处理的动物中，在RP 3V Kiss 1神经元中诱导了反弹爆发放电，并且大多数Kiss 1神经元的超极化阈值为-84.7 mV，这对应于IT去失活的V½。最后，RP 3V中的Kiss 1神经元被μ-和κ-阿片和GABAB受体激动剂超极化，表明这些通路也有助于反弹爆发放电。因此，RP 3V中的Kiss 1神经元表达允许E2依赖性反弹爆发放电的关键通道和受体，并提供驱动排卵前GnRH激增的生物物理底物。
Kisspeptin (Kiss1) neurons in the rostral periventricular area of the third ventricle (RP3V) provide excitatory drive to gonadotropin-releasing hormone (GnRH) neurons to control fertility. Using whole cell patch clamp recording and single-cell (sc)RT-PCR techniques targeting Kiss1-CreGFP or tyrosine hydroxylase (TH)-EGFP neurons, we characterized the biophysical properties of these neurons and identified the critical intrinsic properties required for burst firing in 17β-estradiol (E2)-treated, ovariectomized female mice. One-fourth of the RP3V Kiss1 neurons exhibited spontaneous burst firing. RP3V Kiss1 neurons expressed a hyperpolarization-activated h-current (Ih) and a T-type calcium current (IT), which supported hyperpolarization-induced rebound burst firing. Under voltage clamp conditions, all Kiss1 neurons expressed a kinetically fast Ih that was augmented 3.4-fold by high (LH surge-producing)-E2 treatment. scPCR analysis of Kiss1 neurons revealed abundant expression of the HCN1 channel transcripts. Kiss1 neurons also expressed a Ni(2+)- and TTA-P2-sensitive IT that was augmented sixfold with high-E2 treatment. CaV3.1 mRNA was also highly expressed in these cells. Current clamp analysis revealed that rebound burst firing was induced in RP3V Kiss1 neurons in high-E2-treated animals, and the majority of Kiss1 neurons had a hyperpolarization threshold of -84.7 mV, which corresponded to the V½ for IT de-inactivation. Finally, Kiss1 neurons in the RP3V were hyperpolarized by μ- and κ-opioid and GABAB receptor agonists, suggesting that these pathways also contribute to rebound burst firing. Therefore, Kiss1 neurons in the RP3V express the critical channels and receptors that permit E2-dependent rebound burst firing and provide the biophysical substrate that drives the preovulatory surge of GnRH.