Long-lasting reduction of excitability by a sodium-dependent potassium current in cat neocortical neurons.
Long-lasting reduction of excitability by a sodium-dependent potassium current in cat neocortical neurons.
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DOI：
10.1152/jn.1989.61.2.233
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发表时间：
1989-02
影响因子：
2.5
通讯作者：
P. Schwindt;W. J. Spain;W. Crill
中科院分区：
文献类型：
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作者：
P. Schwindt;W. J. Spain;W. Crill
1.采用体外切片和单微电极电压钳技术，研究了猫感觉运动皮质大V层神经元慢向外向电流的作用及其离子机制。2.阻断Ca~(2+)内流后，外向电流的缓慢松弛(“尾”)发生在(1)引起1-S重复放电或(2)小的1-S去极化电压钳步骤激活新皮质神经元持续性Na+电流INAP之后。当维持激活INAP的去极化时，外向电流逐渐发展，并在数十秒至几分钟的时间内增加幅度。在复极化之后，出现了持续时间相似的外向尾流。TTX可消除慢的外向电流，提示该电流依赖于Na+内流。3.在钙离子内流被阻断后，慢钠依赖外向电流的启动在电流诱发的重复放电过程中引起尖峰频率适应。放电后，Na+依赖电流的衰减导致缓慢的后超极化(SAHP)和兴奋性的持久降低。它还负责对重复的相同电流脉冲的反应习惯化。4.依赖于Na+的尾流具有预期的K+流特性。膜电位超极化和细胞外K+浓度[(K+]0)升高使尾部波幅降低或逆转。5.钾通道阻滞剂TEA(5-10 mM)、毒扁豆碱(5-20微米)和去甲肾上腺素(100微米)可逆性地减少电流尾部。在前一步去极化过程中，这些药剂还导致了更大、更持久的内向电流。对应用阻滞剂前后的电流时间过程的比较表明，尽管它具有缓慢建立和衰减的能力，但依赖于Na+的外向电流的开始发生在适当的阶跃去极化的100ms内。6.在钙离子内流被阻断的情况下，细胞外应用丹曲林钠(30微米)对当前尾巴或相应的SAHP没有明显影响。
1. The function and ionic mechanism of a slow outward current were studied in large layer V neurons of cat sensorimotor cortex using an in vitro slice preparation and single microelectrode voltage clamp. 2. With Ca2+ influx blocked, a slow relaxation ("tail") of outward current followed either (1) repetitive firing evoked for 1 s or (2) a small 1-s depolarizing voltage clamp step that activated the persistent Na+ current of neocortical neurons, INaP. When a depolarization that activated INaP was maintained, an outward current gradually developed and increased in amplitude over a period of tens of seconds to several minutes. An outward tail current of similar duration followed repolarization. The slow outward current was abolished by TTX, indicating it depended on Na+ influx. 3. With Ca2+ influx blocked, the onset of the slow Na+-dependent outward current caused spike frequency adaptation during current-evoked repetitive firing. Following the firing, the decay of the Na+-dependent current caused a slow afterhyperpolarization (sAHP) and a long-lasting reduction of excitability. It also was responsible for habituation of the response to repeated identical current pulses. 4. The Na+-dependent tail current had properties expected of a K+ current. Membrane chord conductance increased during the tail, and tail amplitude was reduced or reversed by membrane potential hyperpolarization and raised extracellular K+ concentration [( K+]0). 5. The current tail was reduced reversibly by the K+ channel blockers TEA (5-10 mM), muscarine (5-20 microM), and norepinephrine (100 microM). These agents also resulted in a larger, more sustained inward current during the preceding step depolarization. Comparison of current time course before and after the application of blocking agents suggested that, in spite of its capability for slow buildup and decay, the onset of the Na+-dependent outward current occurs within 100 ms of an adequate step depolarization. 6. With Ca2+ influx blocked, extracellular application of dantrolene sodium (30 microM) had no clear effect on the current tail or the corresponding sAHP.(ABSTRACT TRUNCATED AT 400 WORDS)