A mammalian two pore domain mechano-gated S-like K+ channel

Patel, Amanda; Honoré, Eric; Maingret, François; Lesage, Florian; Fink, Michel; Duprat, Fabrice; Lazdunski, Michel

doi:10.1093/emboj/17.15.4283

Cited by 608 publications

(864 citation statements)

References 34 publications

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“…Phosphorylation of S333 located at the distal end of the C-terminal cytoplasmic tail is responsible for cAMP-mediated inhibition of TREK-1 (Patel et al, 1998). Since methylxanthines including caffeine and theophylline inhibit phosphodiesterase activity, leading to a gradual increase in intracellular cAMP, we assessed the involvement of cAMP/PKA pathway in the inhibitory action of caffeine and theophylline.…”

Section: Resultsmentioning

confidence: 99%

“…TREK-1 channels are highly expressed in the human CNS (Medhurst et al, 2001) and are targets for pharmacologically important compounds like general anesthetics and neuroprotective drugs like riluzole (Franks and Honore, 2004). TREK-1 is potently inhibited by neurotransmitters that produce an increase in intracellular cAMP and also by those that activate the Gq protein pathway suggesting that probably TREK-1 channels have a central role in the control of excitability by neurotransmitters (Patel et al, 1998;Chemin et al, 2003). Recent in vivo evidence points to TREK-1 as a key target for epileptogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of human TREK-1 channels by caffeine and theophylline

Harinath

Sikdar

2005

Epilepsy Research

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Caffeine (1,3,7-trimethylxanthine) and theophylline (1,3-dimethylxanthine) are used for therapeutic purposes and can cause life-threatening convulsive seizures due to systemic toxicity. The mechanisms for the epileptogenicity of caffeine and theophylline are not clear. TWIK-related K + channels (TREK-1) are highly expressed in the human central nervous system and have a major role in the control of neuronal excitability by regulating the resting membrane potential. In view of their physiological significance, inhibition of TREK-1 channels may be implicated in caffeine-and theophylline-induced seizures. We thus investigated, using whole-cell patch-clamp technique, modulation of hTREK-1 channels expressed in Chinese hamster ovary (CHO) cells by caffeine and theophylline. Caffeine and theophylline produced reversible inhibition of TREK-1 channels in a concentration-dependent manner. The half-maximal inhibitory concentrations (IC 50 ) for caffeine and theophylline were 377 ± 54 M and 486 ± 76 M, respectively. Caffeine and theophylline depolarized the membrane potential of CHO TREK-1 cells in a reversible and concentrationdependent manner. Inhibition by caffeine (5 mM) and theophylline (2 mM) was attenuated in TREK-1 channels with mutation of the PKA consensus sequence at serine 348, suggesting the involvement of cAMP/PKA pathway in the inhibitory process. Inhibition of TREK-1 channels and consequent membrane depolarization may contribute to the convulsive seizures induced by toxic levels of caffeine and theophylline.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of human TREK-1 channels by caffeine and theophylline

Harinath

Sikdar

2005

Epilepsy Research

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“…They are non -selective cation channels (Popp et al 1992 ;Kim 1993), Ca 2+ channels (Lansman et al 1987), Cl --selective anion channels (Tseng 1992 ;Okada 1997), ATP -sensitive K + channels (Van Wagoner & Russo 1992), K + -selective channels (Guharay & Sachs 1984 ;Sigurdson et al 1987), and two -pore domain K + channels called TREK and TRAAK family (Patel et al 1998 ;Bang et al 1999 ;Maingret et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Swelling-activated and arachidonic acid-induced currents are TREK-1 in rat bladder smooth muscle cells

Fukasaku

Kimura

Yamaguchi

2016

FJMS

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Using the perforated patch voltage clamp, we investigated swelling -activated ionic channels (SACs) in rat urinary bladder smooth muscle cells. Hypo -osmotic (60%) bath solution increased a membrane current which was inhibited by the SAC inhibitor, gadolinium. The reversal potential of the hypotonicity -induced current shifted in the positive direction by increasing external K + concentration. The hypotonicity -induced current was inhibited by extracellular acidic pH, phorbol ester and forskolin. These pharmacological properties are identical to those of arachidonic acid -induced current present in these cells, suggesting the presence of TREK -1, a four -transmembrane two pore domain K + channel. Using RT -PCR we screened rat bladder smooth muscles and cerebellum for expression of TREK -1, TREK -2 and TRAAK mRNAs. Only TREK -1 mRNA was expressed in the bladder, while all three were expressed in the cerebellum. We conclude that a mechanosensitive K + channel is present in rat bladder myocytes, which is activated by arachidonic acid and most likely is TREK -1. This K + channel may have an important role in the regulation of bladder smooth muscle tone during urine storage.

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“…The current amplitude of Trek-1 significantly decreases when the external solution osmolarity is increased under whole cell configuration (Honore 2007). Trek-1 channels are open when the actin cytoskeleton is disrupted in cell attached patches (Patel, Honore et al 1998;Honore, Patel et al 2006;Honore 2007), which means that the actin cytoskeleton acts as a tether to regulate the opening of the Trek-1 channels (Honore 2007). The cytoskeletal composition is changed if Trek-1 is overexpressed and membrane protrusions are observed.…”

Section: Trek-1 Potassium Channel and Its Regulationmentioning

confidence: 99%

“…Polyunsaturated fatty acids (PUFAs) like arachidonic acid also activate Trek-1 channels (Patel, Honore et al 1998;Honore 2007). Activation of the channel by arachidonic acid and halothanes has a neuroprotective action during ischemia (Bayliss and Barrett 2008).…”

Section: Trek-1 Potassium Channel and Its Regulationmentioning

confidence: 99%

Silencing Hyper-Excitable Neurons as a Treatment for Status Epilepticus and Temporal Lobe Epilepsy.

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A mammalian two pore domain mechano-gated S-like K+ channel

Cited by 608 publications

References 34 publications

Inhibition of human TREK-1 channels by caffeine and theophylline

Inhibition of human TREK-1 channels by caffeine and theophylline

Swelling-activated and arachidonic acid-induced currents are TREK-1 in rat bladder smooth muscle cells

Silencing Hyper-Excitable Neurons as a Treatment for Status Epilepticus and Temporal Lobe Epilepsy.

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