Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system.
Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system.
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DOI：
10.1016/j.neuroscience.2009.10.028
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发表时间：
2010-07-28
期刊：
影响因子：
3.3
通讯作者：
Rash, J. E.
中科院分区：
文献类型：
--
作者：
Rash, J. E.
关键词：
神经胶质细胞合胞体维持中枢神经系统（CNS）正常神经元电活动所需的离子条件。这些稳态功能中至关重要的是“钾虹吸”，这一过程最初是为了解释每个动作电位期间无髓鞘轴突释放的 K+ 的星形细胞隔离和长距离处理而提出的。有髓轴突需要根本不同的更有效的过程，其中轴突 K+ 流出仅发生在髓鞘下方并封闭在髓鞘内，从而阻止附近星形胶质细胞直接隔离 K+。过量的 K+ 和必然相关的渗透水从轴突进入最内层髓鞘的分子机制尚未得到很好的表征，而在输出端，已知轴突衍生的 K+ 和相关的渗透水被集中在围绕毛细血管并形成胶质细胞界限的星形胶质细胞端脚中的 Kir4.1 和水通道蛋白-4 通道排出。髓磷脂（输入端）和星形胶质细胞端足（输出端）之间是一个巨大的星形胶质细胞“中间体”网络，这些“中间体”通过丰富的间隙连接（包括与髓磷脂）紧密相连，这些间隙连接将多余的 K+ 和水分散到整个神经胶质细胞合胞体中，从而大大减少 K+ 诱导的髓磷脂渗透性膨胀。在这里，我回顾了在无髓鞘中枢神经系统轴突中建立钾虹吸概念的原始报告，总结了我们对轴突跳跃传导过程中 K+ 流出的理解的最新革命，然后描述了有髓轴突对于新描述的电压增强“动态”钾虹吸过程所需的其他组件。如果神经胶质合胞体的几个分子成分中的任何一个受到损害，K+虹吸就会受阻，髓磷脂就会被破坏，轴突跳跃传导就会停止。因此，连接几种中枢神经系统脱髓鞘疾病的共同点是胰岛合胞体内钾虹吸/水运输的破坏。神经胶质离子和水通道的分子鉴定和亚细胞图谱的持续进展将有助于更好地了解中枢神经系统脱髓鞘疾病，并开发改进的治疗方案。
The panglial syncytium maintains ionic conditions required for normal neuronal electrical activity in the central nervous system (CNS). Vital among these homeostatic functions is “potassium siphoning”, a process originally proposed to explain astrocytic sequestration and long-distance disposal of K+ released from unmyelinated axons during each action potential. Fundamentally different, more efficient processes are required in myelinated axons, where axonal K+ efflux occurs exclusively beneath and enclosed within the myelin sheath, precluding direct sequestration of K+ by nearby astrocytes. Molecular mechanisms for entry of excess K+ and obligatorily-associated osmotic water from axons into innermost myelin are not well characterized, whereas at the output end, axonally-derived K+ and associated osmotic water are known to be expelled by Kir4.1 and aquaporin-4 channels concentrated in astrocyte endfeet that surround capillaries and that form the glia limitans. Between myelin (input end) and astrocyte endfeet (output end) is a vast network of astrocyte “intermediaries” that are strongly inter-linked, including with myelin, by abundant gap junctions that disperse excess K+ and water throughout the panglial syncytium, thereby greatly reducing K+-induced osmotic swelling of myelin. Here, I review original reports that established the concept of potassium siphoning in unmyelinated CNS axons, summarize recent revolutions in our understanding of K+ efflux during axonal saltatory conduction, then describe additional components required by myelinated axons for a newly-described process of voltage-augmented “dynamic” potassium siphoning. If any of several molecular components of the panglial syncytium are compromised, K+ siphoning is blocked, myelin is destroyed, and axonal saltatory conduction ceases. Thus, a common thread linking several CNS demyelinating diseases is the disruption of potassium siphoning/water transport within the panglial syncytium. Continued progress in molecular identification and subcellular mapping of glial ion and water channels will lead to a better understanding of demyelinating diseases of the CNS and to development of improved treatment regimens.
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影响因子：
64.8
作者：
CHIU, SY;RITCHIE, JM
通讯作者：
RITCHIE, JM
DOI：
10.1073/pnas.2233464100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Bruzzone, R;Hormuzdi, SG;Monyer, H
通讯作者：
Monyer, H
影响因子：
5.3
作者：
Altevogt, BM;Paul, DL
通讯作者：
Paul, DL
影响因子：
11
作者：
Bähr, M;Andres, F;Dichgans, J
通讯作者：
Dichgans, J
影响因子：
5.3
作者：
Bushong, EA;Martone, ME;Ellisman, MH
通讯作者：
Ellisman, MH