异丙酚对大鼠脊髓背角神经元TTX敏感型钠通道失活和去失活效应的影响

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (6): 614-619.

异丙酚对大鼠脊髓背角神经元TTX敏感型钠通道失活和去失活效应的影响

刘红亮¹, 郭伟韬², 曾因明³, 姚尚龙⁴

¹东南大学附属中大医院麻醉科, 南京 210009, 江苏;
²广东医学院附属医院骨科, 湛江 524023, 广东;
³江苏省麻醉学重点实验室, 徐州 221002, 江苏;
⁴华中科技大学同济医学院附属协和医院麻醉科, 武汉 430030, 湖北

收稿日期:2007-09-11 接受日期:2008-04-16 发布日期:2020-10-14

Effects of propofol on TTX-sensitive voltage-gated sodium channels in rat acutely dissociated spinal dorsal horn neurons

LIU Hong-liang¹, GUO Wei-tao², ZENG Yin-ming³, YAO Shang-long⁴

¹Department of Anesthesiology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, Jiangsu, China;
²Department of Orthopaedics, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524023, Guangdong, China;
³Jiangsu Provincial Key Laboratory of Anesthesiology, Xuzhou 221002, Jiangsu, China;
⁴Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China

Received:2007-09-11 Accepted:2008-04-16 Published:2020-10-14
Contact: LIU Hong-liang, male, Ph.D, lecturer, majors in the mechani sms of general anesthesia and cerebral ischemic injuries. Tel:025-83272060 E-mail:lhl7507@googlemail.com
Supported by:
This project was support ed by the fund of Jiangsu provincial key laboratory of Anesthesiology(KJS06004)

摘要/Abstract

摘要： 目的: 观察异丙酚对急性分离的大鼠脊髓背角神经元TTX敏感型钠通道电流的影响及相关机制。方法: 取出生后7d的雄性SD大鼠,击昏后断头取脊髓腰膨大部位,分离背角神经元,应用全细胞膜片钳记录模式记录钠电流。距离神经细胞100μm施加0.3～30 μmol/L不同浓度的异丙酚,应用-10mV(持续30ms)刺激电压诱发钠电流,求出异丙酚对钠电流的半效抑制浓度(IC₅₀)。观察异丙酚对钠通道失活效应的影响时,应用从-80mV至-20mV的预刺激电压(阶差为10mV,持续30ms),再应用0mV刺激电压(持续30ms)诱发钠电流产生,向神经细胞施加IC₅₀水平的异丙酚。观察异丙酚对钠通道去失活效应的影响时,应用-10mV的预刺激电压(持续30ms),再给予-10mV、持续30ms的刺激电压诱发钠电流产生,两刺激电压的间隔时间为2～24ms。结果: 异丙酚可浓度依赖性地抑制TTX敏感型钠电流,其IC₅₀为(5.35±0.25) μmol/L。钠通道失活实验中,预刺激电压在-60mV到-40mV范围内,IC₅₀水平的异丙酚可显著抑制由刺激电压(0mV)诱发的钠电流(P<0.05)。钠通道去失活实验中,两刺激的间隔时间在2～6ms之间时,IC₅₀水平的异丙酚可显著性抑制由刺激电压(-10mV)诱发的钠电流(P<0.01,P<0.05)。结论: 异丙酚可抑制大鼠脊髓背角电压依赖性钠通道电流,这一作用与促进钠通道的失活和抑制钠通道的去失活有关。

关键词: 异丙酚, 背角神经元, 钠电流

Abstract: AIM: To investigate the effects of propofol on TTX-sensitive voltage-gated sodium currents and its mechanism in acutely dissociated rat spinal dorsal horn neurons.METHODS: Seven-day-old male SD rats were decapitated, a segment of lumbar enlargement of the spinal cord was dissected out, then the dorsal horn neurons were dissociated, and the wholecell patch clamp recording were performed.Propofol of 0.3-30 μmol/L was applied 100 μm apart from the cells.The currents were activated by a 30ms-pulse of-10 mV from holding petential(-80 mV).The inhibitory concentration in 50% of the sodium current amplitude (IC₅₀) value of propofol was estimated.For investigation of sodium channels inactivation, propofol of IC₅₀level was applied, sodium currents were activated by a 30 ms-pulse of 0 mV after a 30 ms-prepulse from-80 mV to-20 mV with a voltage step of 10 mV. For investigation of sodium channels deinactivation, sodium currents were activated by a 30 ms-pulse to-10 mV after a 30 ms-prepulse to-10 mV from holding pontential (-80 mV) under propofol of IC₅₀level, the intervals between the two pulses were from 2 ms to 24 ms.RESULTS: Propofol could inhibit tetrodotoxinsensitive sodium currents in a concentration-dependent manner, the IC₅₀value of propofol was (5.35±0.25) μmol/L.In inactivating sodium channels test, from-60 mV to-40 mV of the prepulse, propofol of IC₅₀level could suppress sodium currents activated by the test pulse significantly (P<0.05);in deinactivating sodium channels test, the currents activated by the test pulse with the intervals from 2ms to 6 ms were significantly suppressed by propofol with IC₅₀ level (P<0.01, P<0.05).CONCLUSION: Propofol inhibited TTX-sensitive voltage-gated sodium currents in rat dorsal horn neurons, which was mediated by facilitating sodium channels inactivating and inhibiting sodium channels from its deinactivation.

Key words: propofol, dorsal horn neuron, sodium current

中图分类号:

R965.2

刘红亮, 郭伟韬, 曾因明, 姚尚龙. 异丙酚对大鼠脊髓背角神经元TTX敏感型钠通道失活和去失活效应的影响[J]. 中国临床药理学与治疗学, 2008, 13(6): 614-619.

LIU Hong-liang, GUO Wei-tao, ZENG Yin-ming, YAO Shang-long. Effects of propofol on TTX-sensitive voltage-gated sodium channels in rat acutely dissociated spinal dorsal horn neurons[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(6): 614-619.

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