Function of KCNQ2 channels at nodes of Ranvier of lumbar spinal ventral nerves of rats.
Function of KCNQ2 channels at nodes of Ranvier of lumbar spinal ventral nerves of rats.
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DOI：
10.1186/s13041-022-00949-0
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发表时间：
2022-07-20
期刊：
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
先前的免疫组织化学研究已经显示KCNQ2通道在有髓神经的Ranvier结（NRs）中表达。然而，这些通道在NR的功能仍然难以捉摸。在本研究中，我们解决了这个问题，直接应用全细胞膜片钳记录在离体制备的大鼠腰脊腹神经的NR。我们发现，去极化电压引起大的非失活外向电流在NR，这是部分抑制KCNQ通道阻滞剂linopirdine和增强KCNQ通道激活剂瑞替加滨。此外，利诺吡啶显着改变NR的内在电生理特性，降低静息膜电位，增加输入电阻，延长AP宽度，降低AP阈值，降低AP振幅。另一方面，瑞替加滨显著降低输入电阻并增加NR处的AP基强度。此外，利诺吡啶通过将单个AP放电转化为许多NR处的多个AP放电来增加NR处的兴奋性。瑞替加滨显著降低跳跃传导速度，利诺吡啶显著增加高刺激频率下的AP成功率。总体而言，KCNQ 2通道在调节大鼠运动神经纤维NR的内在电生理特性和跳跃传导中起重要作用。这些发现可能会为KCNQ2通道的功能缺失突变如何导致人类患者的神经肌肉疾病提供见解。
Previous immunohistochemical studies have shown the expression of KCNQ2 channels at nodes of Ranvier (NRs) of myelinated nerves. However, functions of these channels at NRs remain elusive. In the present study, we addressed this issue by directly applying whole-cell patch-clamp recordings at NRs of rat lumbar spinal ventral nerves in ex vivo preparations. We show that depolarizing voltages evoke large non-inactivating outward currents at NRs, which are partially inhibited by KCNQ channel blocker linopirdine and potentiated by KCNQ channel activator retigabine. Furthermore, linopirdine significantly alters intrinsic electrophysiological properties of NRs to depolarize resting membrane potential, increase input resistance, prolong AP width, reduce AP threshold, and decrease AP amplitude. On the other hand, retigabine significantly decreases input resistance and increases AP rheobase at NRs. Moreover, linopirdine increases excitability at NRs by converting single AP firing into multiple AP firing at many NRs. Saltatory conduction velocity is significantly reduced by retigabine, and AP success rate at high stimulation frequency is significantly increased by linopirdine. Collectively, KCNQ2 channels play a significant role in regulating intrinsic electrophysiological properties and saltatory conduction at NRs of motor nerve fibers of rats. These findings may provide insights into how the loss-of-function mutation in KCNQ2 channels can lead to neuromuscular disorders in human patients.
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DOI：
10.1085/jgp.7.4.473
发表时间：
1925-03-20
期刊：
The Journal of general physiology
影响因子：
--
作者：
Lillie RS
通讯作者：
Lillie RS
DOI：
10.1073/pnas.211431298
发表时间：
2001-10-09
影响因子：
11.1
作者：
Dedek, K;Kunath, B;Steinlein, OK
通讯作者：
Steinlein, OK
影响因子：
5.5
作者：
Schwarz, J. R.;Glassmeier, G.;Bostock, H.
通讯作者：
Bostock, H.
影响因子：
5.5
作者：
HUXLEY, AF;STAMPFLI, R
通讯作者：
STAMPFLI, R
影响因子：
5.5
作者：
Maljevic, Snezana;Wuttke, Thomas V.;Lerche, Holger
通讯作者：
Lerche, Holger