Open AccessRegulation of recombinant human brain tandem P domain K + channels by hypoxia: a role for O 2 in the control of neuronal excitability?
Author(s) -
Kemp P. J.,
Peers C.,
Lewis A.,
Miller Paula
Publication year - 2004
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2004.tb00258.x
Subject(s) - hypoxia (environmental) , potassium channel , membrane potential , chemistry , neuroprotection , ion channel , neuroscience , acidosis , microbiology and biotechnology , inhibitory postsynaptic potential , biophysics , biology , endocrinology , medicine , biochemistry , receptor , organic chemistry , oxygen
The tandem P domain potassium channels, TREK1 and TASK1, are expressed throughout the brain but expression patterns do not significantly overlap. Since normal pO 2 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.