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Volatile anesthetics produce safe, reversible unconsciousness, amnesia and analgesia via hyperpolarization of mammalian neurons. In molluscan pacemaker neurons, they activate an inhibitory synaptic K+ current (IKAn), proposed to be important in general anesthesia. Here we show that TASK and TREK-1, two recently cloned mammalian two-P-domain K+ channels(More)
Mammalian 2P domain K(+) channels are responsible for background or 'leak' K(+) currents. These channels are regulated by various physical and chemical stimuli, including membrane stretch, temperature, acidosis, lipids and inhalational anaesthetics. Furthermore, channel activity is tightly controlled by membrane receptor stimulation and second messenger(More)
Aplysia S-type K+ channels of sensory neurons play a dominant role in presynaptic facilitation and behavioural sensitization. They are closed by serotonin via cAMP-dependent phosphorylation, whereas they are opened by arachidonic acid, volatile general anaesthetics and mechanical stimulation. We have identified a cloned mammalian two P domain K+ channel(More)
Two-pore-domain K(+) (K(2P)) channel subunits are made up of four transmembrane segments and two pore-forming domains that are arranged in tandem and function as either homo- or heterodimeric channels. This structural motif is associated with unusual gating properties, including background channel activity and sensitivity to membrane stretch. Moreover,(More)
TREK-1 is a member of the novel structural class of K(+) channels with four transmembrane segments and two pore domains in tandem (1,2). TREK-1 is opened by membrane stretch and arachidonic acid. It is also an important target for volatile anesthetics (2,3). Here we show that internal acidification opens TREK-1. Indeed, lowering pH(i) shifts the(More)
The biophysical and pharmacological properties of an oxygen-sensitive background K+ current in rat carotid body type-I cells were investigated and compared with those of recently cloned two pore domain K+ channels. Under symmetrical K+ conditions the oxygen-sensitive whole cell K+ current had a linear dependence on voltage indicating a lack of intrinsic(More)
Peripheral and central thermoreceptors are involved in sensing ambient and body temperature, respectively. Specialized cold and warm receptors are present in dorsal root ganglion sensory fibres as well as in the anterior/preoptic hypothalamus. The two-pore domain mechano-gated K(+) channel TREK-1 is highly expressed within these areas. Moreover, TREK-1 is(More)
The two pore domain K(+) channels TREK and TRAAK are opened by membrane stretch. The activating mechanical force comes from the bilayer membrane and is independent of the cytoskeleton. Emerging work shows that mechano-gated TREK and TRAAK are opened by various lipids, including long chain polyunsaturated anionic fatty acids and neutral cone-shaped(More)
TASK-1 encodes an acid- and anaesthetic-sensitive background K(+) current, which sets the resting membrane potential of both cerebellar granule neurons and somatic motoneurons. We demonstrate that TASK-1, unlike the other two pore (2P) domain K(+) channels, is directly blocked by submicromolar concentrations of the endocannabinoid anandamide, independently(More)
The novel structural class of mammalian channels with four transmembrane segments and two pore regions comprise background K+ channels (TWIK-1, TREK-1, TRAAK, TASK, and TASK-2) with unique physiological functions (1-6). Unlike its counterparts, TRAAK is only expressed in neuronal tissues, including brain, spinal cord, and retina (1). This report shows that(More)