Intracellular acidification reduced gap junction coupling between immature rat neocortical pyramidal neurones.

Intracellular acidification reduced gap junction coupling between immature rat neocortical pyramidal neurones.
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细胞内酸化减少了未成熟大鼠新皮质锥体神经元之间的间隙连接耦合。

DOI:
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发表时间:
1996
期刊:
Journal of Physiology
影响因子:
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通讯作者:
Bernd Sutor
Bernd Sutor
中科院分区:
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文献类型:
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作者:
B. Rorig;Gaby Klausa;Bernd Sutor

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1.在大鼠前额叶和感觉运动皮层冠状切片中研究了与间隙连接依赖性染料偶联发育下降相关的锥体神经元电生理特性的发育变化。应用膜片钳技术研究了应用弱有机酸引起的细胞内酸化对神经元染料偶联、电张参数以及突触电位的影响。细胞内pH值的光学监测显示,丙酸钠应用后,酸位移为0.4 - 0.5 pH单位。2.在出生后的前两周,第II-III层神经元之间的染料偶联是突出的。在此期间,用30 mM弱有机酸钠盐预孵育切片,使与注射神经元偶联的细胞数量减少64%。3.在出生后1 - 18天,平均神经元输入电阻显着下降(81.0%)。膜时间常数(τ 0)和第一平衡时间常数(τ 1)也表现出显着的发展下降,分别为25.8%和65.8%。电紧张长度下降34.9%。神经元的电生理特性显示出明显的细胞间变异性,这种变异性随着发育的进行而降低。4.在出生后的前两周,细胞内酸化导致神经元输入电阻平均增加55.9%,电紧张长度平均下降22.2%。在大多数测试的神经元中,膜时间常数降低了约25%。在18日龄大鼠的非偶联神经元中未检测到细胞内酸化诱导的显著电生理效应。5.在发育过程中,半最大振幅下的EPSP宽度大幅减少约50%,而非NMDA受体介导的EPSP成分的上升时间无显著变化。弱有机酸以及差距连接阻断剂1-辛醇均降低兴奋性突触传递,与发育年龄无关。6.我们的结论是,间隙连接通透性调节细胞内pH值在发育中的第II-III层锥体细胞在大鼠新皮层。pH诱导的染料偶联减少与电生理细胞特性变化之间的显著相关性表明间隙连接对未成熟新皮质中的突触整合和信息传递具有显著影响。
1. Developmental changes in electrophysiological properties of pyramidal neurones correlated with the developmental decline in gap junction‐dependent dye coupling were investigated in coronal slices of rat prefrontal and sensorimotor cortex. Effects of intracellular acidification induced by application of weak organic acids on neuronal dye coupling, electrotonic parameters as well as synaptic potentials were examined using the patch clamp technique. Optical monitoring of intracellular pH revealed an acidic shift of 0.4‐0.5 pH units following sodium propionate application. 2. Dye coupling between layer II‐III neurones was prominent during the first two postnatal weeks. During this period, pre‐incubation of slices with 30 mM of the sodium salts of weak organic acids reduced the number of cells coupled to the injected neurones by 64%. 3. Between postnatal days 1 and 18, the mean neuronal input resistance decreased significantly (by 81.0%). Both the membrane time constant (tau 0) and the first equalizing time constant (tau 1) also showed a significant developmental decline of 25.8 and 65.8%, respectively. Electrotonic length decreased by 34.9%. The electrophysiological properties of neurones displayed a pronounced intercellular variability which decreased with on‐going development. 4. During the first two postnatal weeks, intracellular acidification led to a mean increase in neuronal input resistance of 55.9% and a mean decreae in electrotonic length of 22.2%. The membrane time constant was reduced by approximately 25% in the majority of neurones tested. Significant electrophysiological effects induced by intracellular acidification were not detected in uncoupled neurones from 18‐day‐old rats. 5. EPSP width at half‐maximal amplitude showed a substantial reduction of approximately 50%, while rise times of the non‐NMDA receptor‐mediated EPSP components displayed no significant change during development. Both weak organic acids, as well as the gap junction blocker 1‐octanol, reduced excitatory synaptic transmission independent of developmental age. 6. We conclude that gap junction permeability is regulated by intracellular pH in developing layer II‐III pyramidal cells in the rat neocortex. The prominent correlation between pH‐induced reduction in dye coupling and changes in electrophysiological cell properties suggests a significant influence of gap junctions on synaptic integration and information transfer in the immature neocortex.
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