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MTX1 activates KCNQ1. 10 / 10
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"Supporting the premise that IVA effects require the S5 tryptophan, KCNQ1 (which lacks the W) was IVA-insensitive (Fig. 5h, i), whereas KCNQ1 is activated by MTX ."
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"Though Matschke et al. (43) found that MTX activates KCNQ1 and KCNQ4 but not KCNQ2, KCNQ5, or KCNQ2/3, this was likely due to screening for activation at +40 mV, which can fail to identify compounds that activate through shifting the voltage dependence of activation."
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"MTX and CPT1 activated KCNQ1 by hydrogen bonding to the foot of the voltage sensor, a previously unidentified drug site which we also find to be essential for MTX activation of the related KCNQ2/3 channel."
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"MTX and CPT1 activated KCNQ1 by hydrogen bonding to the foot of the voltage sensor, a previously unidentified drug site which we also find to be essential for MTX activation of the related KCNQ2/3 channel."
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"Though Matschke et al. ( xref ) found that MTX activates KCNQ1 and KCNQ4 but not KCNQ2, KCNQ5, or KCNQ2/3, this was likely due to screening for activation at +40 mV, which can fail to identify compounds that activate through shifting the voltage dependence of activation."
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"However, previous studies clearly show that KCNQ1, which lacks the W265 equivalent, is activated by MTX ."
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"Though Matschke et al. ( 43 ) found that MTX activates KCNQ1 and KCNQ4 but not KCNQ2 , KCNQ5 , or KCNQ2 / 3 , this was likely due to screening for activation at +40 mV , which can fail to identify compounds that activate through shifting the voltage dependence of activation ."
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"This was in contrast to a prior report in which MTX was previously found to activate KCNQ1 (a cardiac and epithelial Kv channel) and KCNQ4, while KCNQ2, KCNQ5, and heteromeric KCNQ2/3 channels were concluded to be insensitive ."
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"This was in contrast to a prior report in which MTX was previously found to activate KCNQ1 ( a cardiac and epithelial Kv channel ) and KCNQ4 , while KCNQ2 , KCNQ5 , and heteromeric KCNQ2 / 3 channels were concluded to be insensitive30 ."
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"Two components of the M. oppositifolius leaf extract, mallotoxin (MTX) and 3-ethyl-2-hydroxy-2-cyclopenten-1-one (CPT1), augmented KCNQ1 current by negative shifting its voltage dependence of activation."
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