Activation of potassium conductance by ophiopogonin-D in acutely dissociated rat paratracheal neurones
Activation of potassium conductance by ophiopogonin-D in acutely dissociated rat paratracheal neurones
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DOI：
10.1038/sj.bjp.0703818
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发表时间：
2001-01-01
影响因子：
7.3
通讯作者：
Takahama, K
中科院分区：
文献类型：
--
作者：
Ishibashi, H;Mochidome, T;Takahama, K
1 使用制霉菌素穿孔贴片记录配置，研究了麦冬皂苷-D (OP-D)（一种甾体糖苷和 Bakumondo-to（一种中草药镇咳药）的活性成分）对 2 周龄 Wistar 大鼠气管旁神经节急性分离的神经元的影响。2 在电流钳条件下，OP-D (10 muM) 使气管旁神经节超极化神经元的静息膜电位为 -65.7 至 -73.5 mV。3 当浓度为 1 μM 及以上时，OP-D 浓度依赖性地激活外向电流，同时在电压钳条件下，保持电位为 -40 mV 时膜电导增加。4 OP-D 诱导电流 (IOP-D) 的反转电位为 -79.4 mV，接近 -86.4 的 K+ 平衡电位毫伏。细胞外 K+ 浓度变化 10 倍时，反转电位的变化为 53.1 mV，表明电流由 K+ 携带。5 IOP-D 被细胞外施加 1 mM Ba2+ 阻断 59.0%，但其他 K+ 通道阻断剂，包括 4-氨基吡啶 (3 mM)、apamin (1 muM)、charybdotoxin (0.3 muM)、格列本脲 (1 muM)、甲苯磺丁脲 (0.3 mM) 和四乙铵 (10 mM) 不抑制 6 OP-D 还抑制乙酰胆碱和缓激肽诱导的去极化反应，该反应伴随着动作电位的放电。 7 结果表明，OP-D 可能有助于降低气道副交感神经节神经元的兴奋性，从而通过胆碱能控制气道功能和此外，OP-D 对气管旁神经元的超极化作用以及 K+ 通道的激活可能解释了该药物镇咳作用的部分机制。
1 The effect of ophiopogonin-D (OP-D), a steroidal glycoside and an active component of Bakumondo-to, a Chinese herbal antitussive, on neurones acutely dissociated from paratracheal ganglia of 2-week-old Wistar rats was investigated using the nystatin-perforated patch recording configuration.2 under current-clamp conditions, OP-D (10 muM) hyperpolarized the paratracheal neurones from a resting membrane potential of -65.7 to -73.5 mV.3 At the concentration of 1 muM and above, OP-D concentration-dependently activated an outward current accompanied by an increase in the membrane conductance under voltage-clamp conditions at a holding potential of -40 mV.4 The reversal potential of the OP-D-induced current (IOP-D) was -79.4 mV, which is close to the K+ equilibrium potential of -86.4 mV. The changes in the reversal potential for a 10 fold change in extracellular K+ concentration was 53.1 mV, indicating that the current was carried by K+.5 The IOP-D was blocked by an extracellular application of 1 mM Ba2+ by 59.0%, but other K+ channel blockers, including 4-aminopyridine (3 mM), apamin (1 muM), charybdotoxin (0.3 muM), glibenclamide (1 muM), tolbutamide (0.3 mM) and tetraethylammonium (10 mM), did not inhibit the6 OP-D also inhibited the ACh- and bradykinin-induced depolarizing responses which were accompanied with firing of action potentials.7 The results suggest that OP-D may be of benefit in reducing the excitability of airway parasympathetic ganglion neurones and consequently cholinergic control of airway function and further, that the hyperpolarizing effect of OP-D on paratracheal neurones,lia an activation of K+ channels might explain a part of mechanisms of the antitussive action of the agent.