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Pyraclofos activates KCNQ2. 24 / 24
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"Retigabine, an analogue of flupirtine, shifted the voltage activation of mutated KCNQ2 channels to more hyperpolarized potentials, and also increased the current amplitude [ xref ]."
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"Next, we investigate the mechanism(s) by which the epilepsy-associated mutations R198Q and R214W ( xref ; xref ) alter KCNQ2 channel voltage-dependent activation."
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"However, ethanol did not change the voltage-dependent activation of homomeric Kv7.2 and Kv7.3 channels ( xref ), suggesting that ethanol selectively facilitated the inhibition of Kv7.2 channels with low apparent PI( xref , xref )P 2 binding affinity, but not Kv7.3 channels with high PI( xref , xref )P 2 binding affinity."
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"As expected, the positive controls flupirtine, retigabine, and RL-81 increased the half-maximal voltage-dependent Kv7.2 activation (ΔV 50 ) up to three-fold at 5 μM and thereby provided large shifts in ΔV 50 values."
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"Retigabine, an analogue of flupirtine, shifted the voltage activation of mutated KCNQ2 channels to more hyperpolarized potentials, and also increased the current amplitude [XREF_BIBR]."
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"10 μM CBD also potentiates the voltage activation of KCNQ2 by left-shifting the conductance-voltage (G–V) curve, with an average half maximal activation voltage shift (∆V ) of −10.11 ± 1.08 mV (Fig. 1g)."
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"To test whether these five positively charged residues are essential for the voltage activation of KCNQ2 via the PIP , we then introduced mutations at the PIP binding site in KCNQ2 and recorded the currents of CHO cells expressing WT and mutant KCNQ2."
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"While the mutations R87A and R214A did not change the voltage activation of KCNQ2, K327A reduced the voltage sensitivity of KCNQ2 by right-shifting the G–V curve (Fig. 2c, d)."
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"How do CBD and PIP potentiate the voltage activation of KCNQ2?"
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"10 μM CBD also potentiates the voltage activation of KCNQ2 by left-shifting the conductance-voltage ( G–V ) curve, with an average half maximal activation voltage shift ( ∆V 1/2 ) of −10.11 ± 1.08 mV (Fig.  xref )."
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"Thus, these PTEN mutations did not fully recapitulate the phenotype of native VSPs.When the mutations were introduced simultaneously into PTEN (A126G and TI167/168ET into P and TI loop, respectively), voltage-dependent stimulation caused a decrease in PLCδ -PH-GFP fluorescence at the membrane (Fig. 4a) and substantially inhibited KCNQ2 currents (Fig. 4b and Fig. S3B)."
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"Therefore, both PIP and CBD potentiate the voltage activation of KCNQ2 by enhancing the E–M coupling."
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"To test whether these five positively charged residues are essential for the voltage activation of KCNQ2 via the PIP 2 , we then introduced mutations at the PIP 2 binding site in KCNQ2 and recorded the currents of CHO cells expressing WT and mutant KCNQ2."
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"Therefore, both PIP 2 and CBD potentiate the voltage activation of KCNQ2 by enhancing the E–M coupling."
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"Expression of individual KCNQ subunits in tsA cells revealed voltage independent augmentation of KCNQ2, but not KCNQ1 nor KCNQ3, currents by NEM indicating that this action on SCG M currents likely localizes to KCNQ2."
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"We then ask whether these two sites are both essential for the potentiation of the KCNQ2 voltage activation."
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"We also examined the effect of paroxetine on the voltage-dependent activation of Kv7.2 at a concentration near its IC 50 ."
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"Therefore, both CBD A and CBD B contribute to the potentiation of KCNQ2 voltage activation."
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"This substitution led to a shift of voltage dependent activation of KCNQ2 and a dramatic slowing of activation upon depolarization."
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"The enzyme altered voltage dependence, accelerated activation and slowed deactivation of KCNQ2 and KCNQ3 channels by physically associating with them acting as an auxiliary subunit ( Hessler et al., 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"While the mutations R87A and R214A did not change the voltage activation of KCNQ2, K327A reduced the voltage sensitivity of KCNQ2 by right-shifting the G–V curve (Fig.  xref )."
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"We also examined the effect of paroxetine on the voltage-dependent activation of Kv7.2 at a concentration near its IC ."
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"How do CBD and PIP 2 potentiate the voltage activation of KCNQ2?"
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"A number of antibodies to subunits from different classes of potassium channels were used, including the large conductance Ca 2+ -activated K + channel (BK or KCNMA1), the voltage activated K + channe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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