Dynamic activation of KATP channels in rhythmically active neurons
Dynamic activation of KATP channels in rhythmically active neurons
复制标题
DOI：
10.1111/j.1469-7793.2001.0069k.x
复制
发表时间：
2001-11-15
影响因子：
5.5
通讯作者：
Richter, DW
中科院分区：
文献类型：
--
作者：
Haller, M;Mironov, SL;Richter, DW
1.脑干内的呼吸中枢是最活跃的神经元网络之一，产生持续的节律性活动。这种重要活动的稳定需要有效的过程来进行与活动相关的神经元兴奋性调整。最近的研究表明，电活动与细胞代谢耦合的调节因子包括ATP依赖性K+通道（K-ATP通道），它在常氧过程中不断调节呼吸神经元的兴奋性，并在缺氧过程中不断调节呼吸神经元的兴奋性。2．我们利用单细胞反义RNA扩增-聚合酶链式反应(PCR)技术证明呼吸神经元共表达磺酰脲类受体SUR1和Kir6.2钾通道蛋白。3．对新生小鼠脑干切片制备的节律性活跃吸气神经元的单通道测量表明，K-ATP 通道与每个呼吸周期同步周期性激活。 4．用哇巴因抑制 Na+-K+-ATP 酶，证明通道开放概率的振荡消失，尽管呼吸活动持续较长时间。这些发现表明K-ATP 通道开放概率反映了亚膜域内ATP 浓度的活动依赖性波动。5．我们还检查了细胞外 [K+] 和缺氧的影响。呼吸节律的所有变化（即周期长度和突发持续时间的变化）都会影响 K-ATP 的周期性波动。渠道活动.6.数据表明 K-ATP 通道持续调节中枢呼吸神经元，并有助于神经元兴奋性的周期性调整。这种通道活动的动态调整在高代谢需求范围内进行，从低于生理条件开始一直延伸到能量耗尽的病理情况。
1.The respiratory centre within the brainstem is one of the most active neuronal networks that generates ongoing rhythmic activity. Stabilization of such vital activity requires efficient processes for activity-correlated adjustment of neuronal excitability. Recent, investigations have shown that a regulatory factor coupling electrical activity with cell metabolism comprises ATP-dependent K+ channels (K-ATP channels), which continuously adjust the excitability of respiratory neurons during normoxia and increasingly during hypoxia.2. We used the single-cell antisense RNA amplification-polymerase chain reaction (PCR) technique to demonstrate that respiratory neurons co-express the sulphonylurea receptor SUR1 with the Kir6.2 potassium channel protein.3. Single channel measurements on rhythmically active inspiratory neurons of the brainstem slice preparation of newborn mice revealed that K-ATP channels are periodically activated in synchrony with each respiratory cycle.4. The Na+-K+-ATPase was inhibited with ouabain to demonstrate that oscillations of the channel open probability disappear, although respiratory activity persists for a longer time. Such findings indicate that K-ATP channel open probability reflects activity-dependent fluctuations in the ATP concentration within submembrane domains.5. We also examined the effects of extracellular [K+] and hypoxia. All changes in the respiratory rhythm (i.e. changes in cycle length and burst durations) affected the periodic fluctuations of K-ATP. channel activity.6. The data indicate that K-ATP channels continuously modulate central respiratory neurons and contribute to periodic adjustment of neuronal excitability. Such dynamic adjustment of channel activity operates over a high range of metabolic demands, starting below physiological conditions and extending into pathological situations of energy depletion.