Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones.
Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones.
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DOI：
10.1113/jphysiol.1990.sp017989
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发表时间：
1990-03
期刊：
影响因子：
--
通讯作者：
N. Uchimura;R. North
中科院分区：
文献类型：
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作者：
N. Uchimura;R. North
1. 细胞内记录是从体外保存的大鼠大脑切片中伏隔核中的神经元进行的。 2. 毒蕈碱 (1-100 microM) 使 107 个神经元中的 101 个去极化；这与输入电阻的增加有关。电位变化随着条件超极化而反转极性，并且反转电位与细胞外钾浓度的对数线性相关。 3. 河豚毒素（1 µM）或含有较低水平的钙（0.24 mM，而不是 2.4 mM）、较高水平的镁（5 mM，而不是 1.2 mM）和钴（2 mM）的溶液不会改变毒蕈碱引起的去极化。 4. 当对神经元施加钳制在其静息电位 (‐82 mV) 附近的电压时，毒蕈碱会引起内向电流和斜率电导下降。毒蕈碱引起的电流在钾平衡电位处反转极性。通过假设电压无关的钾电导和内向整流钾电导，可以很好地拟合神经元在 ‐60 和 ‐120 mV 之间的电流-电压关系；毒蕈碱主要降低内向整流器电导。 5. 佛波醇-12,13-二乙酸酯（3 µM）和 5-羟色胺模仿毒蕈碱的作用。由毒蕈碱或5-羟色胺引起的内向电流被佛波酯引起的内向电流阻断。 6、毒蕈碱引起的去极化被哌仑西平竞争性拮抗； 11 nM 的解离常数表明 M1 受体参与其中。 7. 结论是毒蕈碱作用于 M1 受体以降低膜钾电导，并且蛋白激酶 C 的激活可能是中间步骤。
1. Intracellular recordings were made from neurones in the nucleus accumbens in slices from the rat brain maintained in vitro. 2. Muscarine (1‐100 microM) depolarized 101 of 107 neurones; this was associated with an increase in the input resistance. The potential change reversed polarity with conditioning hyperpolarization and the reversal potential was linearly related to the logarithm of the extracellular potassium concentration. 3. The depolarization caused by muscarine was not changed by tetrodotoxin (1 microM) or by a solution that contained lower levels of calcium (0.24 instead of 2.4 mM), higher levels of magnesium (5 instead of 1.2 mM) and cobalt (2 mM). 4. Muscarine caused an inward current and a decrease in slope conductance when applied to neurones voltage clamped near their resting potential (‐82 mV). The current caused by muscarine reversed polarity at the potassium equilibrium potential. The current‐voltage relation of the neurones between ‐60 and ‐120 mV was well fitted by assuming a voltage‐independent potassium conductance and an inward rectifier potassium conductance; muscarine reduced predominantly the inward rectifier conductance. 5. Phorbol‐12,13‐diacetate (3 microM) and 5‐hydroxytryptamine mimicked the action of muscarine. The inward currents caused by muscarine or 5‐hydroxytryptamine were occluded by the inward current evoked by the phorbol ester. 6. The depolarization caused by muscarine was competitively antagonized by pirenzepine; the dissociation constant of 11 nM suggested involvement of the M1 receptor. 7. It is concluded that muscarine acts at M1 receptors to reduce the membrane potassium conductance and that activation of protein kinase C may be an intermediate step.