Regulation of recombinant human brain tandem P domain K+ channels by hypoxia: a role for O2 in the control of neuronal excitability?
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.
Kemp
P J
PJ
School of Biomedical Sciences, Worsley Building, University of Leeds, Leeds, UK. p.z.kemp@leeds.ac.uk
Peers
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Lewis
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Miller
Paula
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D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D007473:Ion Channels; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000096:biosynthesis* / Q000737:chemistry* / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors
D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011994:Recombinant Proteins; C420132:potassium channel subfamily K member 3; D016718:Arachidonic Acid; D010100:Oxygen