Meeks Julian P, Mennerick Steven
Program in Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Hippocampus. 2007;17(11):1100-8. doi: 10.1002/hipo.20344.
Older studies suggest that astrocytes act as potassium electrodes and depolarize with the potassium efflux accompanying neuronal activity. Newer studies suggest that astrocytes depolarize in response to neuronal glutamate release and the activity of electrogenic glial glutamate transporters, thus casting doubt on the fidelity with which astrocytes might sense extracellular potassium rises. Any K(+)-induced astrocyte depolarization might reflect a spatial buffering effect of astrocytes during neuronal activity. For these reasons, we studied stimulus-evoked currents in hippocampal CA1 astrocytes. Hippocampal astrocytes exhibited stimulus-evoked transient glutamate transporter currents and slower Ba(2+)-sensitive inward rectifier potassium (K(ir)) currents. In whole-cell astrocyte recordings, Ba(2+) blocked a very weakly rectifying component of the astrocyte membrane conductance. The slow stimulus-elicited current, like measurements from K(+)-sensitive electrodes under the same conditions, predicted small bulk K(+) increases (<0.5 mM) following the termination of short-stimulus trains. These currents indicate the potential for astrocyte spatial K(+) buffering. However, Ba(2+) did not significantly affect resting K(+) or the K(+) rises detected by the K(+)-sensitive electrode. To test whether local K(+) rises may be significantly higher than those detected by glial recordings or by K(+) electrodes, we assayed EPSCs and fiber volleys, two measures very sensitive to K(+) increases. We found that Ba(2+) had little effect on neuronal axonal or synaptic function during short-stimulus trains, indicating that K(ir)s do not influence local K(+) rises enough, under these conditions to affect synaptic transmission. In conclusion, our results indicate that hippocampal astrocytes are faithful sensors of K(+) rises, but we find little evidence for physiologically relevant spatial K(+) buffering during brief bursts of presynaptic activity.
早期研究表明，星形胶质细胞可作为钾离子电极，并随着伴随神经元活动的钾离子外流而发生去极化。最新研究表明，星形胶质细胞会因神经元释放谷氨酸以及电生性胶质谷氨酸转运体的活动而去极化，从而使人怀疑星形胶质细胞感知细胞外钾离子升高的保真度。任何钾离子诱导的星形胶质细胞去极化可能反映了神经元活动期间星形胶质细胞的空间缓冲作用。基于这些原因，我们研究了海马CA1区星形胶质细胞的刺激诱发电流。海马星形胶质细胞表现出刺激诱发的瞬时谷氨酸转运体电流和较慢的钡离子敏感内向整流钾离子（K(ir)）电流。在全细胞星形胶质细胞记录中，钡离子阻断了星形胶质细胞膜电导的一个非常微弱的整流成分。缓慢的刺激诱发电流，如同在相同条件下用钾离子敏感电极测量的结果一样，预测在短刺激序列终止后细胞外钾离子浓度（K(+)）会有小幅升高（<0.5 mM）。这些电流表明星形胶质细胞具有空间钾离子缓冲的潜力。然而，钡离子对静息状态下的K(+)或钾离子敏感电极检测到的K(+)升高没有显著影响。为了测试局部钾离子升高是否可能显著高于胶质细胞记录或钾离子电极检测到的升高，我们检测了兴奋性突触后电流（EPSCs）和纤维群峰电位，这两种测量方法对钾离子升高非常敏感。我们发现，在短刺激序列期间，钡离子对神经元轴突或突触功能几乎没有影响，这表明在这些条件下，内向整流钾离子通道对局部K(+)升高的影响不足以影响突触传递。总之，我们的结果表明海马星形胶质细胞是细胞外钾离子升高的可靠传感器，但我们几乎没有发现证据表明在突触前活动的短暂爆发期间存在生理相关的空间钾离子缓冲作用。
