Intracellular calcium strongly potentiates agonist-activated TRPC5 channels.
Intracellular calcium strongly potentiates agonist-activated TRPC5 channels.
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DOI：
10.1085/jgp.200810153
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Clapham DE
中科院分区：
文献类型：
--
作者：
Blair NT;Kaczmarek JS;Clapham DE
TRPC 5是钙（Ca 2+）可渗透的非选择性阳离子通道，在几个脑区域中表达，包括海马、小脑和杏仁核。虽然TRPC 5被磷脂酶C受体激活，但精确的信号通路和调节信号仍然不清楚。我们发现，在连续激动剂激活过程中，异源表达的TRPC 5电流以电压依赖性方式增强（在正电位下增强25倍，在负电位下增强25倍）。在这种增强过程中，反向电位、双整流电流-电压关系以及对N-甲基-d-葡萄糖胺等大阳离子的渗透性保持不变。TRPC 5电流增强依赖于细胞外Ca 2+：被Ba 2+或Mg 2+取代会使其消失，而加入10 mM Ca 2+则会使其加速。Ca 2+的作用部位在细胞内，因为同时进行的fura-2成像和膜片钳记录表明，增强在0.01 µM [Ca 2 +]时被触发。当细胞内Ca 2+被紧密缓冲时，这种增强作用被阻止，但是当用含有升高的[Ca 2 +]的内部溶液记录时，这种增强作用被促进。在细胞附着和切除的由内而外的单通道记录中，内部[Ca 2 +]的增加导致通道开放概率增加10-20倍，而单通道电导没有变化。Ca 2+依赖性增强应导致TRPC 5通道激活优先在重复放电或同步神经递质受体激活期间。
TRPC5 is a calcium (Ca2+)-permeable nonselective cation channel expressed in several brain regions, including the hippocampus, cerebellum, and amygdala. Although TRPC5 is activated by receptors coupled to phospholipase C, the precise signaling pathway and modulatory signals remain poorly defined. We find that during continuous agonist activation, heterologously expressed TRPC5 currents are potentiated in a voltage-dependent manner (∼5-fold at positive potentials and ∼25-fold at negative potentials). The reversal potential, doubly rectifying current–voltage relation, and permeability to large cations such as N-methyl-d-glucamine remain unchanged during this potentiation. The TRPC5 current potentiation depends on extracellular Ca2+: replacement by Ba2+ or Mg2+ abolishes it, whereas the addition of 10 mM Ca2+ accelerates it. The site of action for Ca2+ is intracellular, as simultaneous fura-2 imaging and patch clamp recordings indicate that potentiation is triggered at ∼1 µM [Ca2+]. This potentiation is prevented when intracellular Ca2+ is tightly buffered, but it is promoted when recording with internal solutions containing elevated [Ca2+]. In cell-attached and excised inside-out single-channel recordings, increases in internal [Ca2+] led to an ∼10–20-fold increase in channel open probability, whereas single-channel conductance was unchanged. Ca2+-dependent potentiation should result in TRPC5 channel activation preferentially during periods of repetitive firing or coincident neurotransmitter receptor activation.
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DOI：
10.1085/jgp.109.5.647
发表时间：
1997-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cui J;Cox DH;Aldrich RW
通讯作者：
Aldrich RW
影响因子：
34.7
作者：
Burgoyne, Robert D.
通讯作者：
Burgoyne, Robert D.
影响因子：
4.8
作者：
Lambers, TT;Weidema, AF;Bindels, RJM
通讯作者：
Bindels, RJM
影响因子：
5.5
作者：
INOUE, R;ISENBERG, G
通讯作者：
ISENBERG, G
影响因子：
--
作者：
INOUE, R;ISENBERG, G
通讯作者：
ISENBERG, G