Gα14 subunit-mediated inhibition of voltage-gated Ca2+ and K+ channels via neurokinin-1 receptors in rat celiac-superior mesenteric ganglion neurons.
Gα14 subunit-mediated inhibition of voltage-gated Ca2+ and K+ channels via neurokinin-1 receptors in rat celiac-superior mesenteric ganglion neurons.
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Gα14 亚基介导的电压门控 Ca2 和 K 通道通过神经激肽 1 受体在大鼠腹腔肠系膜上神经节神经元的抑制。
DOI：
10.1152/jn.00980.2015
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发表时间：
2016
影响因子：
2.5
通讯作者：
Ruiz-Velasco,Victor
中科院分区：
文献类型：
--
作者：
Sugino,Shigekazu;Farrag,Mohamed;Ruiz-Velasco,Victor
G蛋白调节电压门控Ca2+通道电流（CaV）的机制，特别是CaV2.2和CaV2.3，是电压依赖性（VD）或电压非依赖性（VI）。VD途径通常由Gαi/o和g α s亚家族介导。另一方面，VI抑制调节与g α q亚家族和磷脂酶C刺激下游的信号通路耦合。在大多数研究中，后一种途径已被证明与Gαqand/或g α11蛋白亚基有关。然而，目前还没有研究检测天然表达的Gα14亚单位（Gα q亚家族成员）是否与G蛋白偶联受体（GPCR）结合CaV2.2通道。我们报道了g α14亚基在急性分离的大鼠腹腔-肠系膜上神经节（CSMG）神经元中将P物质(SP)/神经激肽-1 （NK-1）受体通路与CaV2.2通道功能偶联。CSMG神经元暴露于SP后，主要以VD方式阻断CaV2.2电流，对百日咳毒素和霍乱毒素具有抗性，且与Gαq/11无关。然而，g α14亚基的沉默显著减弱了sp介导的Ca2+电流阻滞。在另一组实验中，CSMG神经元暴露于SP导致KCNQ K+ m电流的抑制。g - α14小干扰RNA转染后，sp介导的m电流阻滞显著降低。最后，gtp结合的Gαq/11结合蛋白RGS2的过表达并未改变SP对m电流的阻断，但显著消除了氧tremorine methiotide介导的m电流抑制。综上所述，这些结果证明了一种新的g α14偶联信号通路通过sp刺激的NK-1受体调节CSMG神经元的CaV2.2和m电流。
The mechanisms by which G proteins modulate voltage-gated Ca2+channel currents (CaV), particularly CaV2.2 and CaV2.3, are voltage dependent (VD) or voltage independent (VI). VD pathways are typically mediated by Gαi/oand GαSsubfamilies. On the other hand, VI inhibition modulation is coupled to the Gαqsubfamily and signaling pathways downstream of phospholipase C stimulation. In most studies, this latter pathway has been shown to be linked to Gαqand/or Gα11protein subunits. However, there are no studies that have examined whether natively expressed Gα14subunits (Gαqsubfamily member) couple G protein-coupled receptors (GPCR) with CaV2.2 channels. We report that Gα14subunits functionally couple the substance P (SP)/neurokinin-1 (NK-1) receptor pathway to CaV2.2 channels in acutely dissociated rat celiac-superior mesenteric ganglion (CSMG) neurons. Exposure of CSMG neurons to SP blocked the CaV2.2 currents in a predominantly VD manner that was pertussis toxin and cholera toxin resistant, as well as Gαq/11independent. However, silencing Gα14subunits significantly attenuated the SP-mediated Ca2+current block. In another set of experiments, exposure of CSMG neurons to SP led to the inhibition of KCNQ K+M-currents. The SP-mediated M-current block was significantly reduced in neurons transfected with Gα14small-interference RNA. Finally, overexpression of the GTP-bound Gαq/11binding protein RGS2 did not alter the block of M-currents by SP but significantly abolished the oxotremorine methiodide-mediated M-current inhibition. Taken together, these results provide evidence of a new Gα14-coupled signaling pathway that modulates CaV2.2 and M-currents via SP-stimulated NK-1 receptors in CSMG neurons.
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成年豚鼠腹腔神经节神经元培养物中钾电流及其受毒蕈碱和 P 物质的调节。
影响因子：
2.5
作者：
Vanner,S;Evans,RJ;Matsumoto,SG;Surprenant,A
通讯作者：
Surprenant,A
大鼠交感神经节中的高亲和力 P 物质结合位点。
影响因子：
--
作者：
M. Niwa;K. Shigematsu;L. Plunkett;J. Saavedra
通讯作者：
J. Saavedra
影响因子：
64.8
作者：
BEAN, BP
通讯作者：
BEAN, BP
DOI：
10.1016/s1040-7952(99)80008-1
发表时间：
1999
期刊：
Advances in second messenger and phosphoprotein research
影响因子：
--
作者：
S. Ikeda;K. Dunlap
通讯作者：
S. Ikeda;K. Dunlap
影响因子：
16.2
作者：
ELMSLIE, KS;ZHOU, W;JONES, SW
通讯作者：
JONES, SW