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大鼠背根神经节神经元中温度敏感渗漏 K 电流的特性及 TRAAK、TREK-1 和 TREK2 通道的表达。

Characterization of temperature-sensitive leak K currents and expression of TRAAK, TREK-1, and TREK2 channels in dorsal root ganglion neurons of rats.

机构信息

Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, 901 19TH Street South, BMR II 210, Birmingham, AL, 35294, USA.

出版信息

Mol Brain. 2018 Jul 6;11(1):40. doi: 10.1186/s13041-018-0384-5.

Abstract

Leak K currents are mediated by two-pore domain K (K2P) channels and are involved in controlling neuronal excitability. Of 15 members of K2P channels cloned so far, TRAAK, TREK-1, and TREK-2 are temperature sensitive. In the present study, we show that strong immunoreactivity of TRAAK, TREK-1 and TREK-2 channels was present mainly in small-sized dorsal root ganglion (DRG) neurons of rats. The percentages of neurons with strong immunoreactivity of TRAAK, TREK-1 and TREK-2 channels were 27, 23, and 20%, respectively. Patch-clamp recordings were performed to examine isolated leak K currents on acutely dissociated small-sized rat DRG neurons at room temperature of 22 °C, cool temperature of 14 °C and warm temperature of 30 °C. In majority of small-sized DRG neurons recorded (76%), large leak K currents were observed at 22 °C and were inhibited at 14 °C and potentiated at 30 °C, suggesting the presence of temperature-sensitive K2P channels in these neurons. In a small population (18%) of small-sized DRG neurons, cool temperature of 14 °C evoked a conductance which was consistent with TRPM8 channel activation in cold-sensing DRG neurons. In these DRG neurons, leak K currents were very small at 22 °C and were not potentiated at 30 °C, suggesting that few temperature-sensitive K2P channels was present in cold-sensing DRG neurons. For DRG neurons with temperature-sensitive leak K currents, riluzole, norfluoxetine and prostaglandin F2α (PGE2α) inhibited the leak K currents at both 30 °C and 22 °C degree, and did not have inhibitory effects at 14 °C. Collectively, the observed temperature-sensitive leak K currents are consistent with the expression of temperature-sensitive K2P channels in small-sized DRG neurons.

摘要

漏钾电流由双孔域钾 (K2P) 通道介导,参与控制神经元兴奋性。迄今为止克隆的 15 种 K2P 通道成员中,TRAAK、TREK-1 和 TREK-2 对温度敏感。在本研究中,我们表明,TRAAK、TREK-1 和 TREK-2 通道的强烈免疫反应主要存在于大鼠背根神经节 (DRG) 的小神经元中。具有强免疫反应的 TRAAK、TREK-1 和 TREK-2 通道的神经元百分比分别为 27%、23%和 20%。在 22°C 的室温、14°C 的凉爽温度和 30°C 的温暖温度下,对急性分离的大鼠小 DRG 神经元进行膜片钳记录,以检测分离的漏钾电流。在记录的大多数小 DRG 神经元(76%)中,在 22°C 下观察到大的漏钾电流,在 14°C 下被抑制,在 30°C 下被增强,表明这些神经元中存在温度敏感的 K2P 通道。在一小部分(18%)小 DRG 神经元中,14°C 的凉爽温度会引起与冷感觉 DRG 神经元中 TRPM8 通道激活一致的电导。在这些 DRG 神经元中,22°C 时的漏钾电流非常小,30°C 时不会增强,表明冷感觉 DRG 神经元中存在少量温度敏感的 K2P 通道。对于具有温度敏感漏钾电流的 DRG 神经元,利鲁唑、诺氟西汀和前列腺素 F2α(PGE2α)在 30°C 和 22°C 时均抑制漏钾电流,在 14°C 时无抑制作用。综上所述,观察到的温度敏感漏钾电流与小 DRG 神经元中温度敏感的 K2P 通道表达一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6f0/6035395/63bc21ad2c7c/13041_2018_384_Fig1_HTML.jpg

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