PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 20211602-0 2010 Block of the human ether-a-go-go-related gene (hERG) K+ channel by the antidepressant desipramine. Desipramine 86-97 ETS transcription factor ERG Homo sapiens 47-51 21832094-3 2011 Importantly, desipramine belongs to a group of tricyclic antidepressant compounds that can simultaneously block hERG and inhibit its surface expression. Desipramine 13-24 ETS transcription factor ERG Homo sapiens 112-116 21832094-5 2011 Here, we have studied in detail how desipramine inhibits hERG surface expression. Desipramine 36-47 ETS transcription factor ERG Homo sapiens 57-61 21832094-6 2011 We find a previously unrecognized combination of two entirely different mechanisms; desipramine increases hERG endocytosis and degradation as a consequence of drug-induced channel ubiquitination and simultaneously inhibits hERG forward trafficking from the endoplasmic reticulum. Desipramine 84-95 ETS transcription factor ERG Homo sapiens 106-110 21832094-6 2011 We find a previously unrecognized combination of two entirely different mechanisms; desipramine increases hERG endocytosis and degradation as a consequence of drug-induced channel ubiquitination and simultaneously inhibits hERG forward trafficking from the endoplasmic reticulum. Desipramine 84-95 ETS transcription factor ERG Homo sapiens 223-227 21120454-0 2011 hERG K+ channel-associated cardiac effects of the antidepressant drug desipramine. Desipramine 70-81 ETS transcription factor ERG Homo sapiens 0-4 21120454-8 2011 We found that desipramine reduced hERG currents by binding to a receptor site inside the channel pore. Desipramine 14-25 ETS transcription factor ERG Homo sapiens 34-38 21120454-12 2011 Finally, desipramine triggered apoptosis in cells expressing hERG channels. Desipramine 9-20 ETS transcription factor ERG Homo sapiens 61-65 21120454-13 2011 Desipramine exerts at least four different cellular effects: (1) direct hERG channel block, (2) acute reduction of hERG surface expression, (3) chronic disruption of hERG trafficking, and (4) induction of apoptosis. Desipramine 0-11 ETS transcription factor ERG Homo sapiens 72-76 21120454-13 2011 Desipramine exerts at least four different cellular effects: (1) direct hERG channel block, (2) acute reduction of hERG surface expression, (3) chronic disruption of hERG trafficking, and (4) induction of apoptosis. Desipramine 0-11 ETS transcription factor ERG Homo sapiens 115-119 21120454-13 2011 Desipramine exerts at least four different cellular effects: (1) direct hERG channel block, (2) acute reduction of hERG surface expression, (3) chronic disruption of hERG trafficking, and (4) induction of apoptosis. Desipramine 0-11 ETS transcription factor ERG Homo sapiens 115-119 20211602-2 2010 Since blockade of cardiac human ether-a-go-go-related gene (hERG) channels is an important cause of acquired long QT syndrome, we investigated the acute effects of desipramine on hERG channels to determine the electrophysiological basis for its pro-arrhythmic potential. Desipramine 164-175 ETS transcription factor ERG Homo sapiens 179-183 20211602-3 2010 We examined the effects of desipramine on the hERG channels expressed in Xenopus oocytes using two-microelectrode voltage-clamp techniques. Desipramine 27-38 ETS transcription factor ERG Homo sapiens 46-50 20211602-4 2010 Desipramine-induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. Desipramine 0-11 ETS transcription factor ERG Homo sapiens 115-119 20211602-5 2010 The IC(50) for desipramine needed to block the hERG current in Xenopus oocytes decreased progressively relative to the degree of depolarization. Desipramine 15-26 ETS transcription factor ERG Homo sapiens 47-51 20211602-7 2010 The S6 domain mutations, Tyr-652 located in the S6 domain of the hERG channel reduced the potency of the channel block by desipramine more than a mutation of Phe-656 in the same region. Desipramine 122-133 ETS transcription factor ERG Homo sapiens 65-69 20211602-8 2010 These results suggest that desipramine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects during the clinical administration of desipramine. Desipramine 27-38 ETS transcription factor ERG Homo sapiens 59-63 20211602-8 2010 These results suggest that desipramine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects during the clinical administration of desipramine. Desipramine 180-191 ETS transcription factor ERG Homo sapiens 59-63