Regulatory Mechanisms of Excitability in the Mesencephalic Trigeminal Neurons

中脑三叉神经元兴奋性的调节机制

• 批准号: 14370597
• 负责人: KANG Youngnam
• 金额: $ 8.96万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370597/
• 关键词: mesencephalic trigeminal neuron; primary sensory neuron; masticatory movement; h-channel; Na^+-K^+ pump; A-like current; voltage-dependent Na^+ channel; gap junction channel; 一時感覚ニューロン; 筋紡錘; 歯根膜; 電位依存性K^+チャネル; 4-アミノピリジン; Na^+; K^+ポンプ

(1)Bidirectional interactions between h-channels and Na^+-K^+ pumps in MTN neuronsActivation of h-current (I-h) leads to the generation of two types of ouabain-sensitive Na^+-K^+ pump current (I-p) with temporal profiles similar to those of instantaneous and slow components of I-h, presumably reflecting Na^+-transients in a restricted cellular space. Moreover, the I-p activated by instantaneous I-h can facilitate the subsequent activation of slow I-h. These observations indicate that the interactions are bidirectional and mediated by Na^+ ions. Also following substitution of extracellular Na^+ with Li^+, the tail I-h was markedly reduced in spite of an enhancement of I-h itself, due to a negative shift of the reversal potential for I-h presumably caused by intracellular accumulation of Li^+ ions. This suggests the presence of Na^+-microdomain where the interactions can take place. Consistent with these findings, HCN1/2 subunits and the Na^+-K^+ pump α3 isoform were colocalized in plasm … More a membrane of mesencephalic trigeminal neurons having numerous spines.(2)Impulse trafficking in primary sensory neurons of MTNSimultaneous patch-clamp recordings from the soma and axon hillock(AH) revealed a spike-backpropagation in response to somatic depolarization, and disclosed the spike-initiation site in the stem axon. Repetition of current pulse injection, under the condition of decreasing intracellular concentration gradient of QX-314 from the soma to AH created by QX-314-containing and QX-314-free patch pipettes, unexpectedly attenuated the AH-spike, leaving the soma-spike(S-spike) almost unchanged. When S- or AH-spikes were evoked alternately by injection of current pulses into the soma or AH and by stimulation of the stem axon, bath application of 50 nM TTX first rendered the axonal stimulation ineffective in evoking all-or-nothing axonal spikes, leaving the S- or AH-spikes to be evoked by injection of current pulses with a stepwise increased intensity. Under this condition, spike-backpropagation was no longer seen in the S- or AH-spikes. These observations suggest the presence of low-voltage-activated and highly QX-314- and TTX-sensitive Na^+ channels across the AH and stem axon, which are responsible for both spike-backpropagation and spike-invasion. Furthermore, depending on whether S-spikes were backpropagated or invaded, A-like current was involved in differentially shaping S-spikes, thereby regulating the pattern of S-spike trains in a manner dependent on the origin of spikes. It is likely that somatic inputs or peripherally arising impulses whichever trigger spikes in the stem axon first is forwarded to the central axon, which should be reflected by differentially shaped S-spikes in the soma. Less

(1)MTN神经元H-通道与Na~+-K~+泵的双向相互作用h-电流(I-h)的激活导致两种哇巴因敏感的Na~(++)-K~+泵电流(I-p)的产生，其时间分布类似于I-h的瞬时和慢成分，可能反映了有限细胞空间中的Na~(++)瞬变。此外，瞬时i-h激活的i-p可以促进随后慢i-h的激活。这些观察结果表明，这种相互作用是双向的，并由Na~(++)离子介导。此外，在细胞外Na~(++)被Li~(2+)取代后，尽管I-h本身增强，但尾部I-h显著减少，这可能是由于Li~(2+)在细胞内的积累导致I-h的翻转电位负移所致。这表明存在Na~(++)-微区，在那里可以发生相互作用。与这些发现一致的是，Hcn1/2亚基和Na+-K+泵α3亚型在血浆…中共定位(2)MTN初级感觉神经元的脉冲传输。来自胞体和轴突丘(AH)的同时膜片钳记录显示，体细胞去极化反应出现了棘波反向传播，并揭示了茎轴突中的棘波起始部位。重复电流脉冲注入，在降低QX-314由含QX-314和不含QX-314的贴片吸管产生的胞体到胞体的浓度梯度的条件下，意外地减弱了AH-峰，使胞体-峰(S-峰)几乎不变。当向胞体或胞体注入脉冲电流和刺激轴突交替诱发S峰或AH峰时，先用50 nM TTX浸浴使轴突刺激无效，不能诱发全有或全无轴突放电，而使S峰或AH峰由注入电流脉冲以逐渐增强的强度诱发。在这种情况下，S穗或AH穗中不再出现反向繁殖现象。这些观察结果表明，在AH和茎轴突上存在低电压激活的、对QX-314和TTX高度敏感的Na+通道，这两种通道都是棘波反向繁殖和棘波入侵的原因。此外，根据S穗是被反向繁殖还是被入侵，类A电流参与了S穗的不同形成，从而以一种依赖于穗来源的方式调节S穗序列的模式。躯体输入或外周产生的冲动很可能首先被传递到中央轴突，这应该通过体细胞中不同形状的S棘波来反映。较少

项目成果

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Bidirectional interactions between H-channels and Na+-K+ pumps in mesencephalic trigeminal neurons

• DOI: 10.1523/jneurosci.5641-03.2004
• 发表时间: 2004-04-07
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Kang, YN;Notomi, T;Shigemoto, R
• 通讯作者: Shigemoto, R

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