Changes in osmolality modulate voltage-gated sodium channels in trigeminal ganglion neurons.

Changes in osmolality modulate voltage-gated sodium channels in trigeminal ganglion neurons.
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渗透压的变化调节三叉神经节神经元中的电压门控钠通道。

DOI:
10.1016/j.neures.2009.02.012
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发表时间:
2009-06
影响因子:
2.9
通讯作者:
Cao X
Cao X
中科院分区:
医学4区
文献类型:
--
作者:
Chen L;Liu C;Liu L;Cao X

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电压门控钠通道(VGSC)是一种重要的钠通道,参与多种生理功能。VGSC是否可以通过三叉神经节(TG)神经元中渗透压的变化来调节仍然未知。在本研究中,我们采用全细胞膜片钳技术,检测了低渗和高渗对培养的TG神经元VGSC的影响。我们的数据表明,河豚毒素耐钠电流(TTX-R电流)的存在下,抑制低和高渗溶液。在高渗溶液中,电压依赖性激活和失活曲线均向超极化方向移动,而在低渗溶液中,仅失活曲线向超极化方向移动。瞬时受体电位香草酸4受体(TRPV 4)激动剂模拟低渗对TTX-R电流的抑制作用,TRPV 4受体阻断剂和TRPV 4-/-小鼠TG神经元可明显减弱低渗对TTX-R电流的抑制作用。我们还表明,PKA的抑制选择性衰减低渗诱导的抑制,而PLC和PI 3 K的拮抗选择性衰减高渗诱导的抑制。我们的结论是,虽然低和高渗对VGSC有类似的影响,受体和细胞内信号通路是不同的低与高渗诱导的TTX-R电流的抑制。
Voltage-gated sodium channels (VGSCs) are important channels which participate in many physiological functions. Whether VGSCs can be modulated by changes in osmolality in trigeminal ganglion (TG) neurons remains unknown. In this study, by using whole-cell patch clamp techniques, we tested the effects of hypo- and hypertonicity on VGSCs in cultured TG neurons. Our data show that tetrodotoxin-resistant sodium current (TTX-R current) was inhibited in the presence of hypo- and hypertonic solutions. In hypertonic solutions both voltage–dependent activation and inactivation curves shifted to the hyperpolarizing direction, while in hypotonic solutions only inactivation curve shifted to the hyperpolarizing direction. Transient Receptor Potential Vanilloid 4 receptor (TRPV4) activator mimicked the inhibition of TTX-R current by hypotonicity and the inhibition by hypotonicity was markedly attenuated by TRPV4 receptor blocker and in TRPV4-/- mice TG neurons. We also demonstrate that inhibition of PKA selectively attenuated hypotonicity-induced inhibition, whereas antagonism of PLC and PI3K selectively attenuated hypertonicity-induced inhibition. We conclude that although hypo- and hypertonicity have similar effect on VGSCs, receptor and intracellular signaling pathways are different for hypo- versus hypertonicity-induced inhibition of TTX-R current.
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