Meuth Sven G, Budde Thomas, Kanyshkova Tatyana, Broicher Tilman, Munsch Thomas, Pape Hans-Christian
Institute of Physiology, Otto-von-Guericke-Universität, D-39120 Magdeburg, Germany.
J Neurosci. 2003 Jul 23;23(16):6460-9. doi: 10.1523/JNEUROSCI.23-16-06460.2003.
The thalamocortical network is characterized by rhythmic burst activity during natural sleep and tonic single-spike activity during wakefulness. The change between these two activity modes is partially governed by transmitters acting on leak K+ currents in the thalamus, although the nature of the constituting ion channels is not yet known. In the present study, the contribution of members of the two-pore domain K+ channel family to the leak current was investigated using whole-cell patch-clamp techniques and molecular biological techniques. RT-PCR and in situ hybridization revealed the expression of TWIK-related acid-sensitive K+ channel 1 (TASK 1) and TASK3 channels in the rat dLGN. Voltage-clamp recordings of thalamocortical relay neurons in slice preparations demonstrated the existence of a current component sensitive to the TASK channel blocker bupivacaine, which reversed at the presumed K+ equilibrium potential, showed outward rectification, and contributed approximately 40% to the standing outward current at depolarized values of the membrane potential (-28 mV). The pharmacological profile was indicative of TASK channels, in that the current was sensitive to changes in extracellular pH, reduced by muscarine and increased by halothane, and these effects were occluded by a near-maximal action of bupivacaine. Pharmacological manipulation of this current under current-clamp conditions resulted in a shift between burst and tonic firing modes. It is concluded that TASK1 and TASK3 channels contribute to the muscarine- and halothane-sensitive conductance in thalamocortical relay neurons, thereby contributing to the change in the activity mode of thalamocortical networks observed during the sleep-wake cycle and on application of inhalational anesthetics.
丘脑皮质网络的特征是在自然睡眠期间具有节律性爆发活动，而在清醒期间具有紧张性单峰活动。这两种活动模式之间的变化部分受作用于丘脑漏钾电流的递质调控，尽管构成离子通道的性质尚不清楚。在本研究中，使用全细胞膜片钳技术和分子生物学技术研究了双孔结构域钾通道家族成员对漏电流的贡献。逆转录聚合酶链反应（RT-PCR）和原位杂交显示，大鼠背外侧膝状体核（dLGN）中存在TWIK相关酸敏感钾通道1（TASK 1）和TASK3通道。切片制备中丘脑皮质中继神经元的电压钳记录表明，存在对TASK通道阻滞剂布比卡因敏感的电流成分，该电流在假定的钾平衡电位处反转，表现出外向整流，并且在膜电位去极化值（-28 mV）时对稳定外向电流的贡献约为40%。药理学特征表明该电流为TASK通道，因为该电流对细胞外pH值的变化敏感，受毒蕈碱抑制，受氟烷增强，并且这些效应被布比卡因的近最大作用所阻断。在电流钳条件下对该电流进行药理学操作导致爆发和紧张性放电模式之间的转变。得出的结论是，TASK1和TASK3通道对丘脑皮质中继神经元中对毒蕈碱和氟烷敏感的电导有贡献，从而有助于在睡眠-觉醒周期以及应用吸入性麻醉剂时观察到的丘脑皮质网络活动模式的变化。
