Dual modulation of K channels by thyrotropin-releasing hormone in clonal pituitary cells.
Dual modulation of K channels by thyrotropin-releasing hormone in clonal pituitary cells.
复制标题
克隆垂体细胞中促甲状腺素释放激素对 K 通道的双重调节。
DOI：
10.1073/pnas.82.12.4282
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发表时间：
1985
影响因子：
11.1
通讯作者：
Oxford,GS
中科院分区：
文献类型：
--
作者：
Dubinsky,JM;Oxford,GS
垂体瘤细胞的跨膜电活动可以被刺激或抑制其分泌活动的物质改变。应用膜片钳技术，测定了促甲状腺激素释放激素（TRH）对大鼠垂体瘤细胞GH 3和GH4/C1的静息膜电位、动作电位、跨膜宏观离子电流和单一钙激活钾通道电流的影响。TRH刺激催乳素分泌，引起膜电位的瞬时超极化，随后是一段时间的动作电位频率升高。在单细胞电压钳位和内部透析与含有K+，TRH的应用程序的解决方案，在Ca 2+激活的K电流和电压依赖性的K电流更持久的下降的结果在一个短暂的增加。然而，在细胞内部透析与K+-免费的解决方案，TRH产生内向钙或Ba 2+电流通过电压依赖性钙通道没有变化。对Ca 2+激活和电压依赖性K电流的影响的时间过程分别与超极化和超兴奋性的阶段相关。在应用TRH的全细胞，单一的钙激活的K通道活性增加细胞贴附补丁不直接暴露于TRH。相反，TRH直接应用于切除的膜补丁产生单一的钙激活的K通道行为没有变化。我们的结论是TRH（i）触发细胞内Ca 2+释放，从而打开Ca 2+激活的K通道，（ii）在超兴奋期抑制电压依赖性K通道，从而进一步升高细胞内Ca 2+，（iii）不直接调节Ca通道活性。
Transmembrane electrical activity in pituitary tumor cells can be altered by substances that either stimulate or inhibit their secretory activity. Using patch recording techniques, we have measured the resting membrane potentials, action potentials, transmembrane macroscopic ionic currents, and single Ca2+-activated K channel currents of GH3 and GH4/C1 rat pituitary tumor cells in response to thyrotropin-releasing hormone (TRH). TRH, which stimulates prolactin secretion, causes a transient hyperpolarization of the membrane potential followed by a period of elevated action potential frequency. In single cells voltage clamped and internally dialyzed with solutions containing K+, TRH application results in a transient increase in Ca2+-activated K currents and a more protracted decrease in voltage-dependent K currents. However, in cells internally dialyzed with K+-free solutions, TRH produces no changes in inward Ca2+ or Ba2+ currents through voltage-dependent Ca channels. The time courses of the effects on Ca2+-activated and voltage-dependent K currents correlate with the phases of hyperpolarization and hyperexcitability, respectively. During application of TRH to whole cells, single Ca2+-activated K channel activity increases in cell-attached patches not directly exposed to TRH. In contrast, TRH applied directly to excised membrane patches produces no change in single Ca2+-activated K channel behavior. We conclude that TRH (i) triggers intracellular Ca2+ release, which opens Ca2+-activated K channels, (ii) depresses voltage-dependent K channels during the hyperexcitable phase, which further elevated intracellular Ca2+, and (iii) does not directly modulate Ca channel activity.