Kemp P J, Peers C, Lewis A, Miller Paula
School of Biomedical Sciences, Worsley Building, University of Leeds, Leeds, UK.
J Cell Mol Med. 2004 Jan-Mar;8(1):38-44. doi: 10.1111/j.1582-4934.2004.tb00258.x.
The tandem P domain potassium channels, TREK1 and TASK1, are expressed throughout the brain but expression patterns do not significantly overlap. Since normal pO2 in central nervous tissue is as low as 20 mmHg and can decrease even further in ischemic disease, it is important that the behaviour of human brain ion channels is studied under conditions of acute and chronic hypoxia. This is especially true for brain-expressed tandem P-domain channels principally because they are important contributors to neuronal resting membrane potential and excitability. Here, we discuss some recent data derived from two recombinant tandem P-domain potassium channels, hTREK1 and hTASK1. Hypoxia represents a potent inhibitory influence on both channel types and occludes the activation by arachidonic acid, intracellular acidosis and membrane deformation of TREK1. This casts doubt on the idea that TREK1 activation during brain ischemia might facilitate neuroprotection via hyperpolarising neurons in which it is expressed. Interestingly, hypoxia is unable to regulate alkalotic inhibition of TREK1 suggesting that this channel may be more intimately involved in control of excitability during physiological or pathological alkalosis.
串联P结构域钾通道TREK1和TASK1在整个大脑中均有表达，但表达模式并无显著重叠。由于中枢神经组织中的正常氧分压低至20 mmHg，且在缺血性疾病中甚至会进一步降低，因此在急性和慢性缺氧条件下研究人脑离子通道的行为非常重要。对于在大脑中表达的串联P结构域通道而言尤其如此，主要是因为它们对神经元静息膜电位和兴奋性有重要影响。在此，我们讨论一些来自两种重组串联P结构域钾通道hTREK1和hTASK1的最新数据。缺氧对这两种通道类型均具有强大的抑制作用，并阻断了花生四烯酸、细胞内酸中毒和TREK1膜变形所引起的激活。这使人怀疑在脑缺血期间TREK1激活是否可能通过使其表达的神经元超极化来促进神经保护。有趣的是，缺氧无法调节TREK1的碱中毒抑制作用，这表明该通道可能在生理或病理碱中毒期间对兴奋性控制的参与更为密切。
