Liu Hong-Tao, Tashmukhamedov Bekjan A, Inoue Hana, Okada Yasunobu, Sabirov Ravshan Z
Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
Glia. 2006 Oct;54(5):343-57. doi: 10.1002/glia.20400.
Astrocytes release glutamate upon hyperexcitation in the normal brain, and in response to pathologic insults such as ischemia and trauma. In our experiments, both hypotonic and ischemic stimuli caused the release of glutamate from cultured mouse astrocytes, which occurred with little or no contribution of gap junction hemichannels, vesicle-mediated exocytosis, or reversed operation of the Na-dependent glutamate transporter. Cell swelling and chemical ischemia activated, in cell-attached membrane patches, anionic channels with large unitary conductance (approximately 400 pS) and inactivation kinetics at potentials more positive than +20 mV or more negative than -20 mV. These properties are different from those of volume-sensitive outwardly rectifying (VSOR) Cl- channels, which were also expressed in these cells and exhibited intermediate unitary conductance (approximately 80 pS) and inactivation kinetics at large positive potentials of more than +40 mV. Both maxi-anion channels and VSOR Cl- channels were permeable to glutamate with permeability ratios of glutamate to chloride of 0.21 +/- 0.07 and 0.15 +/- 0.01, respectively. However, the release of glutamate was significantly more sensitive to Gd3+, a blocker of maxi-anion channels, than to phloretin, a blocker of VSOR Cl- channels. We conclude that these two channels jointly represent a major conductive pathway for the release of glutamate from swollen and ischemia-challenged astrocytes, with the contribution of maxi-anion channels being predominant.
在正常大脑中，星形胶质细胞在过度兴奋时会释放谷氨酸，并且在应对诸如缺血和创伤等病理损伤时也会释放谷氨酸。在我们的实验中，低渗刺激和缺血刺激均导致培养的小鼠星形胶质细胞释放谷氨酸，这种释放很少或几乎没有间隙连接半通道、囊泡介导的胞吐作用或钠依赖性谷氨酸转运体反向运转的参与。细胞肿胀和化学性缺血在细胞贴附膜片上激活了具有大的单通道电导（约400 pS）且在电位高于 +20 mV或低于 -20 mV时具有失活动力学的阴离子通道。这些特性不同于容积敏感性外向整流（VSOR）Cl⁻ 通道，VSOR Cl⁻ 通道也在这些细胞中表达，表现出中等的单通道电导（约80 pS）且在大于 +40 mV的大正电位时具有失活动力学。大阴离子通道和VSOR Cl⁻ 通道对谷氨酸均具有通透性，谷氨酸与氯离子的通透率分别为0.21 ± 0.07和0.15 ± 0.01。然而，谷氨酸的释放对大阴离子通道阻滞剂Gd³⁺ 的敏感性明显高于VSOR Cl⁻ 通道阻滞剂根皮素。我们得出结论，这两种通道共同构成了肿胀和缺血应激的星形胶质细胞释放谷氨酸的主要传导途径，其中大阴离子通道的作用占主导地位。
