中文摘要：

利用全细胞膜片钳技术研究乙酰胆碱（acetylcholine，ACh）对大鼠皮层体感区神经元延迟整流钾电流（Ik）的调制作用。结果表明：（1）ACh（0．1、1、10、100μmol／L）对大鼠皮层体感区神经元IK有抑制作用，并具有剂量依赖性关系（P〈0．01）。（2）ACh可使IK激活曲线的斜率变大，并使激活曲线向超极化方向移动。IK激活曲线的半数激活电压（V1/2）和斜率因子（k）分别由给药前的（-41．8±9．7）mV和（30．7±7．2）mV变为给药后的（-122．4±38．6）mV和（42．4±7．0）mV。（3）100μmol／L的N受体拮抗剂筒箭毒碱（tubocurarine）可减弱ACh对IK的抑制作用，在指令电压＋60mV时tubocurarine＋ACh组的IK幅度下降了（16．9±13．8）％（n=8），与10μmol／LACh组引起的（36．5±7．8）％的IK下降幅度相比，有极显著差异（P〈0．01）。10μmol／L的M1受体拮抗剂哌仑西平（pirenzepin）拮抗ACh对IK的抑制作用不明显（n=7，P〉0．05）；而10μmol／L的M3受体拮抗剂4-DAMP可部分拮抗ACh对IK的抑制作用，并且4-DAMP＋ACh组使IK的电流值下降了（26．8±4．7）％（n=6），与ACh组引起的IK电流下降相比，有显著差异（P〈0．05）。（4）蛋白傲酶C（proteinkinase C，PKC）阻断剂chelerythrine拮抗ACh对k的抑制作用，PKC激动剂PDBu可增强ACh对k的抑制作用（P〈0．05）。综上所述，ACh对大鼠皮层体感区神经元IK的抑制作用主要是通过烟碱受体（nAChRs）和M8受体介导，并经过PKC信号途径。

英文摘要：

The modulation of ACh on delayed rectifier-like potassium currents （Ik） was studied in freshly dissociated cerebral cortical neurons using the whole-cell patch-clamp technique. Wistar rats between 10- and 14-day old of both sexes were used. After rats were decapitated, their brains were quickly removed, iced, and then manually cut into 400μm slices. Slices were then incubated for 0.5 h at 32℃ in a buffered artificial cerebrospinal fluid （ACSF） bubbled with 95% 02, 5% CO2. Slices were then removed into buffered ACSF containing protease （0.5 mg/ml） at 32℃. After 30 rain of enzyme digestion, tissue was rinsed three times in the buffered saline. Then the enzyme-treated slices were mechanically dissociated with a graded series of fire-polished Pasteur pipettes. The cell suspension was then plated into a 35 mm dish and placed on the stage of a Olympus inverted microscope. For whole-cell recordings of currents, standard voltage-clamp techniques were used. Neurons were held at -80 mV, and the IK was evoked by 2 000 ms depolarizing voltage commands to potential between -40 mV and ＋60 mV in 10 mV steps applied at a frequency of 0.5 Hz. It was found that the inhibitory effect of ACh （0.1, 1, 10, 100μmol/L） on IK was dose-dependent. It was also found that ACh affected the activation process of IK significantly, i.e., the activation curve of IK was characterized by half-activation potential of （-41.8±9.7） mV and a slope factor of （30.7±7.2） mV in the cortical neurons and they were changed to （-122.4±38.6） mV and （42.4±7.0） mV, respectively, after giving ACh （10μmol/L）. Tubocurarine （100μmol/L） antagonized the inhibitory effect of ACh on IK, and the drop of currents varied from the control value of （36.5±7.8）% to （16.9±13.8）% （n=8, P〈0.01）. 4-DAMP （10μmol/L） blocked the inhibitory effect of ACh on IK, and the currents reduced from the control value of （36.5±7.8）% to （26.8±4.7）% （n=6, P〈0.05）. Pirenzepin did not antagonize the inhibition