IndraLab

Statements

KCNH2 activates Kr. 46 / 46
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"Consistent with this notion, accelerated I Kr / hERG deactivation (as a response to extracellular acidosis) has previously been shown to reduce the protective role of I Kr early in diastole and decrease AP excitation threshold in a human ventricular AP model."
33475719
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"HERG channels underlie the delayed-rectifier K + channel current (I Kr), which is crucial for membrane repolarization and therefore termination of the cardiac action potential."
30530765
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"HERG produces I Kr the rapidly repolarizing potassium current in cardiomyocytes XREF_BIBR."
23812503
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"HERG channels underlie the cardiac delayed rectifier current, I Kr, and their unique voltage dependent gating properties are critical to normal repolarization during the cardiac action potential."
22586397
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"Another LQTS subtype, LQT2, is caused by mutations in the potassium-channel gene KCNH2 that lead to a reduction in I Kr."
28883014
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"Using patch clamp to study Na + and Ca 2 + currents, as well as whole-cell current clamp to measure AP, they found that LQTS cells have tendencies toward prolonged AP duration, smaller Na + current de[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26578113
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"LQT2 has mutations in KCNH2, a human ether-a-go-go-related gene (hERG) that mediates rapid delayed-rectifier potassium current I Kr, which is important for the repolarization phase of the AP [XREF_BIBR]."
33255277
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"As it can not be proven that LR 50, dofetilide is equal in dog and human, however, only its relative consistency across drugs can be assumed (Black and Leff 1983); it could also generally be interpreted as a higher net contribution of hERG mediated I Kr current to cardiac repolarization."
28097003
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"HERG1 channels produce I Kr XREF_BIBR; XREF_BIBR, a potassium current important in repolarizing the ventricular action potential 23."
25158096
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"Alterations in hERG mediated I Kr current, whether drug induced or a result of the over 200 naturally occurring mutations of this channel, may induce or contribute to the development of long QT syndrome."
20156596
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"In addition, sustained functional reentry is seen to accelerate in cardiomyocytes ' monolayers infected by hERG to increase their I Kr."
28096699
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"The KCNH2 gene encodes the alpha-subunit of the voltage gated potassium channel and mediates the rapidly activating component of the delayed rectifying potassium current (I Kr)."
28146053
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"Analysis of the current generated following transfection of the mutated channel into human embryonic kidney (HEK) cells showed that the mutation shifted inactivation of the KCNH2 channels out of the range of the action potential, thus producing a large gain of function in I Kr."
20042373
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"Changes in hERG 1a/1b subunit abundance modulate I Kr kinetics, magnitude, and drug sensitivity."
36496073
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"In these previous studies, we demonstrated that the underlying electrophysiological mechanism is secondary to the effect of the K897T polymorphism to accentuate the loss of function of delayed rectifier potassium current (I Kr) caused by other mutations in KCNH2."
22338672
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"The hERG (human ether-a-go-go related gene) potassium channel (Kv11.1), encoded by the KCNH2 gene, underlies the rapidly activating delayed rectifier K + current (I Kr)."
24392021
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"The former terminology stems from the finding that HERG underlies a component of I Kr, a " delayed rectifier " current in cardiac muscle."
9607937
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"Erg channels are widely expressed, including the brain and heart, where cardiac herg1 underlies the I Kr current in the heart and its dysfunction can lead to dangerous arrhythmias."
12135768
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"XREF_BIBR Despite the evidence that heteromeric hERG 1a/1b channels underlie cardiac I Kr, we know little about the gating and pharmacological properties of these channels, how hERG 1a/1b channels differ from hERG 1a homomers, or what role the hERG 1b subunit might play in disease."
18776039
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"Mutations in the KCNQ1 and HERG genes cause the Long QT Syndromes, LQTS1 and LQTS2, due to reductions in the cardiac repolarizing I Ks and I Kr currents, respectively."
20348026
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"In the heart, HERG K + channel subunits mediate a delayed rectifier K + current (I Kr) that aids cellular repolarization."
10102937
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"XREF_BIBR, XREF_BIBR The hERG potassium channel underlies the delayed rectifier potassium current (I Kr), and is the most common potassium channel associated with drug induced QT prolongation."
31911979
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"Heterologous expression studies have shown that the N588K mutation in KCNH2 dramatically increases I Kr density and reduces the affinity of the channel to d-sotalol by 20-fold."
20042373
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"Therefore, the investigators could conclude reasonably that increased I Kr, mediated by activation of HERG potassium channels, compensated for the action potential prolonging effects of ATX-II."
19121809
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"Mutations in KCNH2 cause a reduction of I Kr current, through mechanisms similar to the effects exhibited by KCNQ1 mutations on I Ks current."
22895603
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"As shown in Fig. 6, overexpression of HERG markedly increased I Kr, as recorded during action potential clamp, and suppressed APD alternans during rapid pacing."
12581710
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"Native I Kr and hERG channels exhibit sensitivity to pharmacological blockade by diverse drugs, including both Class Ia and Class III antiarrhythmic agents; excessive pharmacological inhibition of I Kr / hERG leads to acquired long QT syndrome."
23300672
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"As previously discussed, the common mechanism by which the majority of drugs produce QT prolongation and thus increased risk of TdP is through I Kr blockade by Kv11.1 inhibition, as well as possible inhibition of Kv11.1 channel trafficking [40] ."
34360853
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"K v 11.1 (also known as hERG) underlies the rapidly-activating delayed-rectifier K + current (I Kr ), which plays a major role in cardiac ventricular repolarization."
36752166
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"Potassium channels encoded by human ether-a-go-go-related gene (hERG) mediate the cardiac rapid delayed rectifier K + current (I Kr), which participates in ventricular repolarization and has a protective role against unwanted premature stimuli late in repolarization and early in diastole."
25318749
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"The WT HERG produced an I (Kr)-like, E-4031-sensitive conductance with an inward rectification."
10517660
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"LQTS2 is caused by mutations in KCNH2, a gene whose protein product contributes to I Kr (also known as HERG), which is the predominant repolarizing potassium current in CMs."
28992755
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"This study also found Kv11.1 hERG 1a protein expression was reduced compared to controls, suggesting reduced functional expression of I Kr may be one mechanism contributing to HF induced I Kr downregulation."
25596015
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"KCNH2 deletion using CRISPR simultaneously abolished I Kr and the hERG1 NP signal in hiPSC-CMs."
36626562
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"In contrast, several hERG channel activators have been shown to enhance I Kr and shorten the APD and thus might have potential antiarrhythmic effects against pathological LQTS."
33829343
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"HERG E1039X mutation caused an incomplete loss-of-function in ' I Kr '."
29449639
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"Acetylcholine, a selective agonist of I Ach shortens the APD in atrial but not ventricular myocytes whereas E-4031, a selective blocker of I Kr mediated by hERG, prolonged APD in ventricular CMs but not atrial CMs."
29075196
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"Functional expression studies have demonstrated that mutations in the KCNH2 gene cause a reduction of I Kr current."
18606002
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"In the heart, the rapidly activating component of the delayed rectifying K + current (I Kr) is mediated by HERG1 [XREF_BIBR]."
22075718
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"Virtually all data on PIP 2 modulation of the EAG channel family comes from a single gene, the human Erg subfamily channel Erg1 (hErg1, Kv11.1), which underlies the I Kr current critical to cardiac action potential repolarization."
26503718
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"However, it was recently reported that coassembly of HERG and MiRP1 (minK related peptide) subunits induces a current with properties almost exactly like I Kr recorded in cardiac myocytes (Abbott et al. 1999)."
10694252
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"The HERG (human ether-a-go-go-related gene, alternative nomenclature KCNH2) is responsible for channels mediating I Kr which plays an important role in ventricular repolarization."
21779290
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"A reduction of I Kr caused by long QT syndrome (LQTS)-associated mutations in KCNH2 can induce ventricular arrhythmia and cause sudden cardiac death."
20544339
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"The rapidly activating delayed rectifier K + channel (I Kr) is encoded by the human ether-a-go-go -related gene (hERG), which is important for the repolarization of the cardiac action potential."
28495999
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"HERG overexpression upregulates I Kr in NRVM."
20947828
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"Work in several laboratories has contributed to our understanding of how the gating mechanisms of HERG channels enable I Kr to fulfill its physiological role in the heart."
10828248