Hyperpolarization-activated Cyclic Nucleotide-gated Channels May Contribute to Regional Anesthetic Effects of Lidocaine
Hyperpolarization-activated Cyclic Nucleotide-gated Channels May Contribute to Regional Anesthetic Effects of Lidocaine
复制标题
超极化激活的环核苷酸门控通道可能有助于利多卡因的局部麻醉作用
DOI：
10.1097/aln.0000000000000557
复制
发表时间：
2015-03-01
期刊：
影响因子：
8.8
通讯作者：
Chen, Xiangdong
中科院分区：
文献类型：
--
作者：
Zhou, Cheng;Ke, Bowen;Chen, Xiangdong
背景：局部麻醉剂（例如，利多卡因）除抑制钠通道外还抑制超极化激活的环核苷酸门控（HCN）通道。然而，HCN通道在体内区域麻醉中的确切作用仍然是hailey.Methods：坐骨神经阻滞和鞘内麻醉使用利多卡因在野生型和HCN 1通道敲除（HCN 1（-/-））小鼠。测定利多卡因的EC 50和1%利多卡因作用时间。在电生理记录中，记录了利多卡因对背根神经节神经元HCN通道电流、电压门控钠通道电流和神经膜特性的影响。在坐骨神经阻滞和鞘内麻醉中，利多卡因触觉感觉阻滞的EC 50（2 g von Frey纤维）在HCN 1（-/-）小鼠中显著增加，而利多卡因用于针刺阻滞的EC 50不受影响。HCN 1（-/-）小鼠坐骨神经阻滞和鞘内麻醉的1%利多卡因持续时间显著缩短（n = 10）。ZD 7288（HCN阻滞剂）能显著延长1%利多卡因坐骨神经阻滞的持续时间（n = 10）。在坐骨神经阻滞中，福斯可林（升高环磷酸腺苷以增强HCN 2）可显著缩短1%利多卡因针刺阻滞的持续时间（n = 10）。在电生理记录中，利多卡因可非选择性地抑制大、小背根神经节神经元（n = 5 ~ 6）的HCN通道和钠通道电流。同时，利多卡因引起HCN 1（-/-）小鼠背根神经节神经元膜超极化和输入阻力增加，但对大背根神经节神经元无影响。利多卡因可通过抑制HCN通道而改变神经元的膜特性。
Background: Local anesthetics (e.g., lidocaine) have been found to inhibit hyperpolarization-activated cyclic nucleotide-gated (HCN) channels besides sodium channels. However, the exact role of HCN channels in regional anesthesia in vivo is still elusive.Methods: Sciatic nerve block and intrathecal anesthesia were performed using lidocaine in wild-type and HCN1 channel knockout (HCN1(-/-)) mice. EC50 of lidocaine and durations of 1% lidocaine were determined. In electrophysiologic recordings, effects of lidocaine on HCN channel currents, voltage-gated sodium channel currents, and neural membrane properties were recorded on dorsal root ganglia neurons.Results: In both sciatic nerve block and intrathecal anesthesia, EC50 of lidocaine for tactile sensory blockade (2 g von Frey fiber) was significantly increased in HCN1(-/-) mice, whereas EC50 of lidocaine for pinprick blockade was unaffected. Durations of 1% lidocaine were significantly shorter in HCN1(-/-) mice for both sciatic nerve block and intrathecal anesthesia (n = 10). ZD7288 (HCN blocker) could significantly prolong durations of 1% lidocaine including pinprick blockade in sciatic nerve block (n = 10). Forskolin (raising cyclic adenosine monophosphate to enhance HCN2) could significantly shorten duration of pinprick blockade of 1% lidocaine in sciatic nerve block (n = 10). In electrophysiologic recordings, lidocaine could nonselectively inhibit HCN channel and sodium channel currents both in large and in small dorsal root ganglia neurons (n = 5 to 6). Meanwhile, lidocaine caused neural membrane hyperpolarization and increased input resistance of dorsal root ganglia neurons but not in large dorsal root ganglia neurons from HCN1(-/-) mice (n = 5-7).Conclusions: These data indicate that HCN channels may contribute to regional anesthetic effects of lidocaine. By inhibiting HCN channels, lidocaine could alter membrane properties of neurons.