Activation of steroid-sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats.
Activation of steroid-sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats.
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DOI：
10.1111/j.1471-4159.2011.07441.x
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发表时间：
2011-11
影响因子：
4.7
通讯作者：
Valenzuela CF
中科院分区：
文献类型：
--
作者：
Zamudio-Bulcock PA;Everett J;Harteneck C;Valenzuela CF
瞬时受体电位melastatin 3（TRPM 3）激活，最近描述的成员melastatin亚家族的阳离子可渗透的TRP通道的功能的影响，已开始阐明在最近几年。TRPM 3被类固醇硫酸双烯醇酮（PregS）激活的发现为该通道的生理作用提供了新的线索。例如，TRPM 3激活增强β胰腺细胞的胰岛素分泌，诱导血管平滑肌收缩，并且还参与有害热的检测。尽管已在发育和成熟大脑的多个区域检测到TRPM 3表达，但人们对TRPM 3在大脑生理学中的作用知之甚少。在这里，我们证明了TRPM 3类固醇敏感通道在发育中的小脑皮质的丰富表达。我们还表明，TRPM 3样通道表达在新生儿浦肯野细胞（PC）的突触。我们最近发现，PregS增强自发谷氨酸释放到新生儿PC在一段时间的活跃的谷氨酸能突触形成;我们现在表明，这种影响PregS是由TRPM 3样通道介导的。最近发现的TRPM 3拮抗剂甲芬那酸可阻断PregS对谷氨酸释放的作用。其他TRPM 3激动剂（硝苯地平和表孕烯醇酮硫酸盐）模拟了Pregs对谷氨酸释放的作用，但TRMP 3无活性类固醇（孕酮）却没有模拟。我们的研究结果确定TRPM 3通道作为发育中大脑中神经递质传递的新型调节剂。
The functional implications of transient receptor potential melastatin 3 (TRPM3) activation, the most recently described member of the melastatin subfamily of cation permeable TRP channels, have begun to be elucidated in recent years. The discovery of TRPM3 activation by the steroid pregnenolone sulfate (PregS) has shed new light on the physiological role of this channel. For example, TRPM3 activation enhances insulin secretion from β pancreatic cells, induces contraction of vascular smooth muscle, and is also involved in the detection of noxious heat. Although TRPM3 expression has been detected in several regions of the developing and mature brain, little is known about the roles of TRPM3 in brain physiology. Here, we demonstrate the abundant expression of TRPM3 steroid-sensitive channels in the developing cerebellar cortex. We also show that TRPM3-like channels are expressed at glutamatergic synapses in neonatal Purkinje cells (PCs). We recently showed that PregS potentiates spontaneous glutamate release onto neonatal PCs during a period of active glutamatergic synapse formation; we now show that this effect of PregS is mediated by TRPM3-like channels. Mefenamic acid, a recently discovered TRPM3 antagonist, blocked the effect of PregS on glutamate release. The PregS effect on glutamate release was mimicked by other TRPM3 agonists (nifedipine and epipregnanolone sulfate) but not by a TRMP3-inactive steroid (progesterone). Our findings identify TRPM3 channels as novel modulators of glutamatergic transmission in the developing brain.
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影响因子：
20.1
作者：
Naylor J;Li J;Milligan CJ;Zeng F;Sukumar P;Hou B;Sedo A;Yuldasheva N;Majeed Y;Beri D;Jiang S;Seymour VA;McKeown L;Kumar B;Harteneck C;O'Regan D;Wheatcroft SB;Kearney MT;Jones C;Porter KE;Beech DJ
通讯作者：
Beech DJ
影响因子：
7.3
作者：
Klose, Chihab;Straub, Isabelle;Harteneck, Christian
通讯作者：
Harteneck, Christian
影响因子：
9.8
作者：
Conde-Agudelo A;Romero R;Kusanovic JP
通讯作者：
Kusanovic JP
影响因子：
4.8
作者：
Jung, S;Mühle, A;Plant, TD
通讯作者：
Plant, TD
影响因子：
3.1
作者：
JANICKI, PK;SIEMBAB, D;KRZASCIK, P
通讯作者：
KRZASCIK, P