Han Jaehee, Gnatenco Carmen, Sladek Celia D, Kim Donghee
Department of Physiology and Biophysics, Finch University of Health Sciences/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.
J Physiol. 2003 Feb 1;546(Pt 3):625-39. doi: 10.1113/jphysiol.2002.032094.
Magnocellular neurosecretory cells (MNCs) were isolated from the supraoptic nucleus of rat hypothalamus, and properties of K(+) channels that may regulate the resting membrane potential and the excitability of MNCs were studied. MNCs showed large transient outward currents, typical of vasopressin- and oxytocin-releasing neurons. K(+) channels in MNCs were identified by recording K(+) channels that were open at rest in cell-attached and inside-out patches in symmetrical 150 mM KCl. Eight different K(+) channels were identified and could be distinguished unambiguously by their single-channel kinetics and voltage-dependent rectification. Two K(+) channels could be considered functional correlates of TASK-1 and TASK-3, as judged by their single-channel kinetics and high sensitivity to pH(o). Three K(+) channels showed properties similar to TREK-type tandem-pore K(+) channels (TREK-1, TREK-2 and a novel TREK), as judged by their activation by membrane stretch, intracellular acidosis and arachidonic acid. One K(+) channel was activated by application of pressure, arachidonic acid and alkaline pH(i), and showed single-channel kinetics indistinguishable from those of TRAAK. One K(+) channel showed strong inward rectification and single-channel conductance similar to those of a classical inward rectifier, IRK3. Finally, a K(+) channel whose cloned counterpart has not yet been identified was highly sensitive to extracellular pH near the physiological range similar to those of TASK channels, and was the most active among all K(+) channels. Our results show that in MNCs at rest, eight different types of K(+) channels can be found and six of them belong to the tandem-pore K(+) channel family. Various physiological and pathophysiological conditions may modulate these K(+) channels and regulate the excitability of MNCs.
从大鼠下丘脑视上核分离出大细胞神经分泌细胞（MNCs），并研究了可能调节MNCs静息膜电位和兴奋性的钾离子通道特性。MNCs表现出大的瞬时外向电流，这是血管加压素和催产素释放神经元的典型特征。通过记录在对称的150 mM KCl中细胞贴附式和内面向外膜片中静息时开放的钾离子通道，鉴定了MNCs中的钾离子通道。鉴定出了八种不同的钾离子通道，可通过它们的单通道动力学和电压依赖性整流明确区分。根据它们的单通道动力学和对细胞外pH值的高敏感性判断，两种钾离子通道可被视为TASK-1和TASK-3的功能相关物。根据它们被膜拉伸、细胞内酸中毒和花生四烯酸激活的情况判断，三种钾离子通道表现出与TREK型双孔钾离子通道（TREK-1、TREK-2和一种新型TREK）相似的特性。一种钾离子通道在施加压力、花生四烯酸和碱性细胞内pH值时被激活，并且其单通道动力学与TRAAK的无法区分。一种钾离子通道表现出强烈的内向整流，其单通道电导与经典内向整流器IRK3相似。最后，一种其克隆对应物尚未确定的钾离子通道在生理范围内对细胞外pH值高度敏感，类似于TASK通道，并且是所有钾离子通道中活性最高的。我们的结果表明，在静息状态下的MNCs中，可以发现八种不同类型的钾离子通道，其中六种属于双孔钾离子通道家族。各种生理和病理生理条件可能调节这些钾离子通道并调节MNCs的兴奋性。
