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KCNH2 activates calcium(2+). 28 / 28
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"In this way, hERG inactivation allows sodium and calcium conductances to maintain ventricular depolarization for more than a whopping 300 ms (compared to <3 ms for a neuronal action potential)."
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"We previously demonstrated that the stimulation of Kv11.1 activity produces significant Ca entry in breast cancer cells [35]."
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"Further, we showed that HERG overexpression in C C myotubes also produces an increase in MuRF1 protein abundance and, interestingly, in both basal [Ca ]i and calpain activity ."
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"The cytotoxic chemotherapeutics doxorubicin and epirubicin, known to cause cardiomyopathy, preferentially reduced Ca (i) (2+) transient amplitude and sarcoplasmic reticulum (SR) Ca (2+) content, whereas Torsade de Pointes (TdP) inducers and potent hERG channel blockers (amiodarone, cisapride, dofetilide, E-4031 and terfenadine) predominately suppressed diastolic Ca (i) (2+) and contraction rate, and prolonged Ca (i) (2+) transient duration."
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"The data support that ECCE contributes to the HERG-induced increase in [Ca ]i in C C myotubes; however, HERG may also modulate other Ca entry pathways."
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"Using C2C12 myotubes transduced with HERG-encoded virus, we have shown that overexpression of the HERG channel increases basal intracellular calcium concentration and calpain activity 3 ."
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"Instead, using the SERCA blocking agent thapsigargin with our Fura2 assay, we discovered that the HERG-mediated increase in calcium occurs through modulation of intracellular calcium stores."
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"38 This is because hERG block delays repolarization, increasing the probability of L-type calcium current triggering extra beats called early afterdepolarizations (EADs), which can initiate TdP."
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"Here we demonstrate that HERG overexpression enhances the increase in [Ca ]i that occurs with caffeine treatment in myotubes; and this effect is blocked by inhibitory concentrations of ryanodine, suggesting that HERG modulates RyR1 activity."
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"However, single cell calcium imaging reveals that the HERG-mediated increase in calcium is inhibited by treatment with the IP3 receptor antagonist Xestospongin-C."
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"Additionally, IP3 signaling could also be responsible for the HERG enhanced increase in [Ca ]i during Tg treatment."
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"Blockage of hERG channel by BmKKx2 causing the Ca 2+ concentration decrease during the erythroid differentiation of K562 cells."
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"Bepridil is a potent hERG blocker that also blocks L-type calcium and peak and late sodium currents at higher concentrations (Crumb et al., 2016)."
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"In this work, the inhibition of hERG channel currents by scorpion toxin BmKKx2 was found to decrease the intracellular Ca 2+ concentration during the differentiation process of K562 cells (XREF_FIG)."
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"In addition we have also reveal that hERG1 stimulation induces an increase in intracellular calcium that is required for cyclin E2 degradation."
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"We further postulate that HERG overexpression may constitutively enhance SOCE activity perhaps by lowering the concentration/availability of free calcium in the SR and/or by the decreased inhibition of STIM1 resulting from lowered Casq1."
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"Next, we analyzed by immunoblotting potential hERG stimulated signaling pathways in K562 cells by analyzing the activities of the Ca 2+ effector proteins CaMKIIs (Ca 2+ / calmodulin dependent protein kinase II isoforms) and their downstream target cdc2 (cyclin dependent kinase 1, CDK1) (XREF_FIG)."
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"Importantly, hERG1 inhibition by E4031 (1 microM) prevented radiation induced CaMKIIs activation and cdc2 inactivation (XREF_FIG, 5 th -8 th lane and XREF_FIG, closed bars) suggesting that Ca 2+ signals modulated by hERG1 were required for radiation induced CaMKIIs activation and inhibition of cdc2."
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"Indeed, the pure hERG channel blocker, dofetilide, was shown to increase both QTc (heart rate-corrected QT) and J-T peak c (heart rate-corrected J-T peak ) intervals, while the strong L-type Ca 2+ and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Therefore, we tested the hypothesis that, stimulation of hERG1 activity could promote calcium influx in breast cancer cells."
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"Moreover, the KCNH2 potassium channels may directly regulate the characteristics of sodium and calcium channels XREF_BIBR."
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"Having established that NS1643 treatment increases intracellular calcium levels, we investigated on the role of hERG1 driven calcium entry on cyclin E2 degradation."
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"It has been hypothesized that the reason may be the higher expression of L-type Ca 2+ channels observed invitro in hiPSC-CMs compared to adult cells, reiterated in : " Bepridil is a potent hERG blocker that also blocks L-type calcium and peak and late sodium currents at higher concentrations."
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"Given the potentially important role of Ca in modulation of skeletal muscle health and atrophy, we sought to understand the mechanism whereby HERG expression elevates basal [Ca ]i in C C myotubes ."
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"As it is dependent on Ca 2+ transient, the EMw was also more sensitive than AP prolongation in distinguishing between pure hERG blockers and multichannel compounds also blocking the calcium current."
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"HERG contributes to phase three repolarization by opposing the depolarizing Ca 2+ influx during the plateau phase [6]."
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"In addition, the blockage of hERG potassium channel by toxin BmKKx2 was able to decrease the intracellular Ca 2+ concentration during the K562 cell differentiation, providing an insight into the mechanism of hERG potassium channel regulating this cellular process."
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"Thus, although HERG is inducing a greater increase in [Ca ]i in response to depolarization, this effect does not appear to be the result of increased Cav1.1 activity at 48 h after transduction."
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