右美托咪定
蓝斑
超极化(物理学)
哌唑嗪
育亨宾
可乐定
羟甲唑啉
化学
药理学
生物物理学
生物
内分泌学
肾上腺素能受体
中枢神经系统
受体
立体化学
生物化学
敌手
镇静
核磁共振波谱
作者
Tsai‐Hsien Chiu,Mei-Jane Chen,Yea-Ru Yang,Jia-Jang Yang,Fuk‐Tan Tang
标识
DOI:10.1016/0014-2999(95)00417-j
摘要
The action of dexmedetomidine on rat locus coeruleus neurones was examined using intracellular recordings from the in vitro brain slice preparation. Concentrations of dexmedetomidine from 1 to 1000 nM were tested. At 30 nM, dexmedetomidine produced complete inhibition of firing of all neurones tested (n = 21); this was associated with a 13 mV hyperpolarization (range 2.2–29.7 mV, n = 21) and a 27% reduction in input resistance (range 11.1–46.2%, n = 17). The dexmedetomidine responses reached a plateau phase between 100 and 1000 nM. Based on single-cell recordings, the hyperpolarizing potency of dexmedetomidine was found to be 6 times greater than that of clonidine (n = 10). The reversal potential for the dexmedetomidine-induced hyperpolarization was − 106.9 ± 1.7 mV (n = 9), a value similar to the K+ equilibrium potential; hyperpolarization was blocked by both CsCl and BaCl2. The effect of dexmedetomidine was antagonized by yohimbine, with a dissociation equilibrium constant of 30 nM. In contrast, prazosin, the α1-, α2B- and α2C-adrenoceptor subtype-preferring ligand, did not inhibit the dexmedetomidine effect. Our results also show that low concentrations of oxymetazoline (10–300 nM), an α2A-adrenoceptor subtype-selective drug, cause profound inhibition of neuronal activity in the locus coeruleus. These data therefore suggest that dexmedetomidine binds to α2A-adrenoceptors on the cell membrane of neurones of the locus coeruleus and that this leads to opening of the inwardly rectifying K+ channels, resulting in the observed hyperpolarization of the membrane.
科研通智能强力驱动
Strongly Powered by AbleSci AI