Volume-sensitive chloride channels in mouse cortical neurons: characterization and role in volume regulation
Volume-sensitive chloride channels in mouse cortical neurons: characterization and role in volume regulation
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DOI：
10.1111/j.1460-9568.2005.04006.x
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发表时间：
2005-03-01
影响因子：
3.4
通讯作者：
Okada, Y
中科院分区：
文献类型：
--
作者：
Inoue, H;Mori, S;Okada, Y
由于持续肿胀会导致细胞损伤并常常导致细胞死亡，因此容量调节是神经元和非神经元细胞的重要生理功能。脑细胞肿胀不仅在各种病理条件下而且在生理突触传递过程中也被观察到。据报道，体积敏感阴离子通道在许多细胞类型渗透膨胀后发生的调节体积减少中发挥重要作用。在这项研究中，使用双光子激光扫描显微镜和膜片钳技术，我们发现原代培养的小鼠皮质神经元在暴露于低渗溶液期间短暂肿胀和Cl-电流激活后表现出调节体积减少。 Cl-通道阻滞剂或K+通道阻滞剂可抑制调节容量的减少。膨胀激活的Cl-电流表现出外向整流、大正电位下的时间依赖性失活、低场阴离子渗透性序列、中间单一电导以及对体积敏感Cl-通道的已知阻断剂的敏感性。因此，可以得出结论，体积敏感的外向整流Cl-通道的活性在皮质神经元细胞体积的控制中发挥作用。
Because persistent swelling causes cell damage and often results in cell death, volume regulation is an important physiological function in both neuronal and non-neuronal cells. Brain cell swelling has been observed not only in various pathological conditions but also during physiological synaptic transmissions. Volume-sensitive anion channels have been reported to play an important role in the regulatory volume decrease occurring after osmotic swelling in many cell types. In this study, using a two-photon laser scanning microscope and patch-clamp techniques, we found that mouse cortical neurons in primary culture exhibit regulatory volume decrease after transient swelling and activation of Cl- currents during exposure to a hypotonic solution. The regulatory volume decrease was inhibited by Cl- channel blockers or K+ channel blockers. Swelling-activated Cl- currents exhibited outward rectification, time-dependent inactivation at large positive potentials, a low-field anion permeability sequence, an intermediate unitary conductance and sensitivity to known blockers of volume-sensitive Cl- channels. Thus, it is concluded that the activity of the volume-sensitive outwardly rectifying Cl- channel plays a role in the control of cell volume in cortical neurons.