Nikolic Ljiljana, Bataveljic Danijela, Andjus Pavle R, Moldovan Ivana, Nedeljkovic Miodrag, Petkovic Branka
J Biol Rhythms. 2014 Dec;29(6):442-55. doi: 10.1177/0748730414559126.
Hibernation is a dormant state of some animal species that enables them to survive harsh environmental conditions during the winter seasons. In the hibernating state, preservation of neuronal rhythmic activity at a low level is necessary for maintenance of suspended forms of behavior. As glial cells support rhythmic activity of neurons, preservation of brain function in the hibernating state implies accompanying modification of glial activity. A supportive role of glia in regulating neuronal activity is reflected through the activity of inwardly rectifying K+ channels (Kir). Therefore, we examined electrophysiological response, particularly Kir current response, of glial cells in mixture with neurons acutely isolated from active and hibernating land snail Helix pomatia. Our data show that hibernated glia have significantly lower inward current density, specific membrane conductance, and conductance density compared with active glia. The observed reduction could be attributed to the Kir currents, since the Ba2+-sensitive Kir current density was significantly lower in hibernated glia. Accordingly, a significant positive shift of the current reversal potential indicated a more depolarized state of hibernated glia. Data obtained show that modification of glial current response could be regulated by serotonin (5-HT) through an increase of cGMP as a secondary messenger, since extracellular addition of 5-HT or intracellular administration of cGMP to active glia induced a significant reduction of inward current density and thus mimicked the reduced response of hibernated glia. Lower Kir current density of hibernated glia accompanied the lower electrical activity of hibernated neurons, as revealed by a decrease in neuronal fast inward Na+ current density. Our findings reveal that glial response is reduced in the hibernating state and suggest seasonal modulation of glial activity. Maintenance of low glial activity in hibernation could be important for preservation of brain rhythmic activity and survival of the animal.
冬眠是一些动物物种的一种休眠状态,使它们能够在冬季恶劣的环境条件下生存。在冬眠状态下,维持低水平的神经元节律活动对于维持行为的暂停形式是必要的。由于神经胶质细胞支持神经元的节律活动,因此在冬眠状态下维持脑功能意味着神经胶质活动会随之发生改变。胶质细胞在调节神经元活动中的支持作用通过内向整流钾通道(Kir)的活性得以体现。因此,我们研究了从活跃和冬眠的陆地蜗牛皱疤琥珀螺急性分离出的与神经元混合的胶质细胞的电生理反应,特别是Kir电流反应。我们的数据表明,与活跃的胶质细胞相比,冬眠的胶质细胞的内向电流密度、比膜电导和电导密度显著更低。观察到的降低可能归因于Kir电流,因为冬眠的胶质细胞中Ba2 +敏感的Kir电流密度显著更低。相应地,电流反转电位的显著正向偏移表明冬眠的胶质细胞处于更去极化的状态。所获得的数据表明,5-羟色胺(5-HT)可通过增加作为第二信使的环磷酸鸟苷(cGMP)来调节胶质电流反应,因为向活跃的胶质细胞胞外添加5-HT或胞内给予cGMP会导致内向电流密度显著降低,从而模拟了冬眠的胶质细胞的降低反应。如神经元快速内向钠电流密度降低所揭示的那样,冬眠的胶质细胞较低的Kir电流密度伴随着冬眠神经元较低的电活动。我们的研究结果表明,在冬眠状态下胶质反应降低,并提示了胶质活动的季节性调节。冬眠期间维持低水平的胶质活动对于维持脑节律活动和动物生存可能很重要。