IndraLab

Statements

KCNH2 activates Kr. 55 / 55
| 55
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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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"The voltage-dependent hERG channels underlie I Kr which represents the principal repolarizing current at the end of the plateau phase, owing to unique gating properties with slow activation kinetics a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18336833
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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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"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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"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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"The WT HERG produced an I (Kr)-like, E-4031-sensitive conductance with an inward rectification."
10517660
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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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"HERG produces I Kr the rapidly repolarizing potassium current in cardiomyocytes XREF_BIBR."
23812503
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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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"HERG E1039X mutation caused an incomplete loss-of-function in ' I Kr '."
29449639
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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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"HERG overexpression upregulates I Kr in NRVM."
20947828
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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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"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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"The hERG channel, which produces the I Kr current, is robustly blocked by a large class of drugs."
19762090
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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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"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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"HERG (human Ether-a-go-go Related Gene)-encoded potassium channels underlie the cardiac rapid delayed rectifier (I Kr ) potassium current, which is a major target for antiarrhythmic agents and diverse non-cardiac drugs linked to the drug-induced form of long QT syndrome."
37765012
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"These agents block hERG, which mediates the cardiac I Kr current that regulates repolarization in both human atria and ventricles."
36924945
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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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"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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"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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"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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"In the heart, HERG K + channel subunits mediate a delayed rectifier K + current (I Kr) that aids cellular repolarization."
10102937
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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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"Last, the sympathetic regulation of the rapid delayed rectifier I Kr , driven by the HERG channel, is more elusive."
23811359
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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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"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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"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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"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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"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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"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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"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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"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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"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
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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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"Together, these findings imply that male hiPSC-CMs have a larger I Ks current reserve to counteract I Kr current reductions by hERG channel blockers, resulting in smaller responses to I Kr blockers.We[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
31201864
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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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"The N588K mutation in KCNH2 led to loss of normal rectification of I Kr at physiological range of voltages resulting in large gain of function during phase 2 and 3 of the action potential, leading to [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18378319
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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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"In addition, in a previous simulation study of HERG mutations associated with the long QT syndrome, Clancy and Rudy [22] commented that simulating loss of C-type inactivation of HERG alone reduced APD[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15325285
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"2 It was also reported that HERG produces the I Kr -like currents that are sensitively blocked by the I Kr blockers when was expressed in the human cell line."
15324906
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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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"HERG underlies the repolarizing current, I Kr , and direct hERG block by the drug is thought to be the cause of the TdP ( Kiehn, Lacerda, Wible, & Brown, 1996; Mohammad et al., 1997; Rampe et al., 199[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15950494
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"Furthermore, although KCNH2 is a major contributor to the I Kr current responsible for myocardial repolarization in the human heart, repolarization in murine cardiomyocytes is much faster and mediated[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
31484079
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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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"Since I Kr is mediated at least in part by heteromeric ERG1 channels [5–8] , electrophysiological experiments were performed on heterologously expressed homo- and heteromeric ERG1a/ERG1b channels."
20188738
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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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"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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"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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"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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"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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"Inhibition of the potassium channel encoded by the human ether-a-go-go-related gene (HERG) KCNH2 , which mediates the potassium current I Kr , was indicated as a primary correlate with drug-induced ar[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27095424
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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 hERG cardiac potassium channel underlies I Kr and is inhibited by a wide variety of compounds."
20153443