IndraLab

Statements



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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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"By contrast, none of the previously mentioned experimental condition (alone or in combination) was able to recover Kv7.2 p.G310Δ10 function (Figures 4A,B; Table 1), possibly suggesting that the G310-K319 region deleted by the mutation is critically involved in Kv7.2 currents functional modulation by PIP and/or CaM.To further investigate variant-induced changes in PIP -dependent Kv7.2 currents modulation, PIP levels were decreased upon co-expression of the voltage-dependent phosphatase DrVSP."

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"Both CaM and PIP potentiate Kv7.2 currents; thus, the possibility existed that the observed mutation-induced LoF effects were dependent on alterations in the PIP /CaM-dependent Kv7.2 current regulation."

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"Since all the current KCNQ2 structures are in decoupled conformation with activated VSDs and a closed PD , how PIP and antiepileptic drugs activate KCNQ2 by enhancing the E–M coupling remains largely unknown.In this report, we use cryo-electron microscopy (cryo-EM) and electrophysiology to study the modulation mechanisms of KCNQ2 E–M coupling by the activators PIP , CBD, and HN37."

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"For KCNQ2 homomers, we have previously shown that their small macroscopic currents are due to their low apparent affinity for PIP 2; thus, an increase in tonic PIP 2 abundance in the membrane increase[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Recent progress elucidated that PIP modulate KCNQ2/KCNQ3 channel opening by interacting synergistically with a minimum of four cytoplasmic domains (Hernandez et al. 2008a; Choveau et al. 2018)."

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"How do CBD and PIP potentiate the voltage activation of KCNQ2?"

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"38 The R144 residue is located in S , immediately above this PIP binding site, suggesting its possible role in PIP -dependent modulation of Kv7.2 channels gating."