IndraLab

Statements

Phosphatidylinositol phosphate inhibits KCNK2. 10 / 10
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"These data, combined with previous studies of PLD2 activation of TREK-1, led us to propose a model where PIP 2 can directly antagonize TREK-1."
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"However, crude increases in PIP 2 concentration after initial activation have been shown to inactivate TREK-1 in cell culture, consistent with our direct PIP 2 antagonism playing a role in vivo."
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"Exogenous PIP 2 application was reported to reduce TREK1 response to various activating stimuli, including acidosis and membrane stretch."
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"Later the same authors reported that PIP application can also produce TREK-1 inhibition (Chemin et al, 2007)."
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"Our assay shows PIP 2 binds with high affinity (0.87 mM) but surprisingly can directly antagonize TREK-1 in liposomes."
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"Because PIP 2 appears to antagonize TREK-1, it is unclear whether binding of small molecules is directly competing or if there are multiple conformations that lead to antagonism."
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"For example, PIP 2 inhibits TREK-1 while PA activates and PA saturation inhibits K ir 2 channels while PIP 2 activates (Box 1) [XREF_BIBR, XREF_BIBR]."
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"Furthermore, in liposomes, PIP caused inhibition of TREK-1 K flux in the presence of PG, suggesting that PIP might cause inhibition by competitive displacement of the strongly activatory lipids such as PG or PA (Cabanos et al., 2017)."
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"So why does PIP 2 antagonize TREK-1 in liposomes when PA and PG are activating?"
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"Channels like TREK-1 that are agonized by PA and directly inhibited by PIP 2 [XREF_BIBR] are likely the most affected since PEtOH and PIP 2 would combine to antagonize PA, and PA is in relatively low concentrations in the cell."
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