KCNH2A561V Heterozygous Mutation Inhibits KCNH2 Protein Expression via The Activation of UPR Mediated by ATF6
Physiol Res. 2023 Nov 28;72(5):621-631.ABSTRACTThe potassium channel protein KCNH2 is encoded by KCNH2 gene, and there are more than 300 mutations of KCNH2. Unfolded protein response (UPR) is typically initiated in response to an accumulation of unfolded and/or misfolded proteins in the endoplasmic reticulum (ER). The present study aimed to explore the UPR process and the role of activating transcription factor 6 (ATF6) in the abnormal expression of potassium voltage-gated channel subfamily H member 2 (KCNH2)A561V. The wild-type (wt) KCNH2 and A561V mutant KCNH2 was constructed with his-tag. The 293 cells were used and div...
Source: Physiological Research - November 28, 2023 Category: Physiology Authors: B Chen L Tan D Chen X Wang J Liu X Huang Y Wang S Huang F Mao J Lian Source Type: research
KCNH2A561V Heterozygous Mutation Inhibits KCNH2 Protein Expression via The Activation of UPR Mediated by ATF6
Physiol Res. 2023 Nov 28;72(5):621-631.ABSTRACTThe potassium channel protein KCNH2 is encoded by KCNH2 gene, and there are more than 300 mutations of KCNH2. Unfolded protein response (UPR) is typically initiated in response to an accumulation of unfolded and/or misfolded proteins in the endoplasmic reticulum (ER). The present study aimed to explore the UPR process and the role of activating transcription factor 6 (ATF6) in the abnormal expression of potassium voltage-gated channel subfamily H member 2 (KCNH2)A561V. The wild-type (wt) KCNH2 and A561V mutant KCNH2 was constructed with his-tag. The 293 cells were used and div...
Source: Physiological Research - November 28, 2023 Category: Physiology Authors: B Chen L Tan D Chen X Wang J Liu X Huang Y Wang S Huang F Mao J Lian Source Type: research
KCNH2A561V Heterozygous Mutation Inhibits KCNH2 Protein Expression via The Activation of UPR Mediated by ATF6
Physiol Res. 2023 Nov 28;72(5):621-631.ABSTRACTThe potassium channel protein KCNH2 is encoded by KCNH2 gene, and there are more than 300 mutations of KCNH2. Unfolded protein response (UPR) is typically initiated in response to an accumulation of unfolded and/or misfolded proteins in the endoplasmic reticulum (ER). The present study aimed to explore the UPR process and the role of activating transcription factor 6 (ATF6) in the abnormal expression of potassium voltage-gated channel subfamily H member 2 (KCNH2)A561V. The wild-type (wt) KCNH2 and A561V mutant KCNH2 was constructed with his-tag. The 293 cells were used and div...
Source: Physiological Research - November 28, 2023 Category: Physiology Authors: B Chen L Tan D Chen X Wang J Liu X Huang Y Wang S Huang F Mao J Lian Source Type: research
KCNH2A561V Heterozygous Mutation Inhibits KCNH2 Protein Expression via The Activation of UPR Mediated by ATF6
Physiol Res. 2023 Nov 28;72(5):621-631.ABSTRACTThe potassium channel protein KCNH2 is encoded by KCNH2 gene, and there are more than 300 mutations of KCNH2. Unfolded protein response (UPR) is typically initiated in response to an accumulation of unfolded and/or misfolded proteins in the endoplasmic reticulum (ER). The present study aimed to explore the UPR process and the role of activating transcription factor 6 (ATF6) in the abnormal expression of potassium voltage-gated channel subfamily H member 2 (KCNH2)A561V. The wild-type (wt) KCNH2 and A561V mutant KCNH2 was constructed with his-tag. The 293 cells were used and div...
Source: Physiological Research - November 28, 2023 Category: Physiology Authors: B Chen L Tan D Chen X Wang J Liu X Huang Y Wang S Huang F Mao J Lian Source Type: research
Voltage-gated potassium channels KCNQs: Structures, mechanisms, and modulations
Biochem Biophys Res Commun. 2023 Nov 9;689:149218. doi: 10.1016/j.bbrc.2023.149218. Online ahead of print.ABSTRACTKCNQ (Kv7) channels are voltage-gated, phosphatidylinositol 4,5-bisphosphate- (PIP2-) modulated potassium channels that play essential roles in regulating the activity of neurons and cardiac myocytes. Hundreds of mutations in KCNQ channels are closely related to various cardiac and neurological disorders, such as long QT syndrome, epilepsy, and deafness, which makes KCNQ channels important drug targets. During the past several years, the application of single-particle cryo-electron microscopy (cryo-EM) techniqu...
Source: Biochemical and Biophysical Research communications - November 17, 2023 Category: Biochemistry Authors: Yuan Huang Demin Ma Zhenni Yang Yiwen Zhao Jiangtao Guo Source Type: research
In Vivo Base Editing of Scn5a Rescues Type 3 Long QT Syndrome in Mice
CONCLUSIONS: These findings show that in vivo AAV9-ABEmax editing can correct the variant Scn5a allele, effectively ameliorating arrhythmia phenotypes. Our results offer a proof of concept for the treatment of hereditary arrhythmias.PMID:37965733 | DOI:10.1161/CIRCULATIONAHA.123.065624 (Source: Circulation)
Source: Circulation - November 15, 2023 Category: Cardiology Authors: Man Qi Shuhong Ma Jingtong Liu Xujie Liu Jingjing Wei Wen-Jing Lu Siyao Zhang Yun Chang Yongshuai Zhang Kejia Zhong Yuting Yan Min Zhu Yabing Song Yundai Chen Guoliang Hao Jianbing Wang Li Wang Andrew S Lee Xiangbo Chen Yongming Wang Feng Lan Source Type: research
In Vivo Base Editing of Scn5a Rescues Type 3 Long QT Syndrome in Mice
CONCLUSIONS: These findings show that in vivo AAV9-ABEmax editing can correct the variant Scn5a allele, effectively ameliorating arrhythmia phenotypes. Our results offer a proof of concept for the treatment of hereditary arrhythmias.PMID:37965733 | DOI:10.1161/CIRCULATIONAHA.123.065624 (Source: Circulation)
Source: Circulation - November 15, 2023 Category: Cardiology Authors: Man Qi Shuhong Ma Jingtong Liu Xujie Liu Jingjing Wei Wen-Jing Lu Siyao Zhang Yun Chang Yongshuai Zhang Kejia Zhong Yuting Yan Min Zhu Yabing Song Yundai Chen Guoliang Hao Jianbing Wang Li Wang Andrew S Lee Xiangbo Chen Yongming Wang Feng Lan Source Type: research
Structural modeling of hERG channel –drug interactions using Rosetta
The human ether-a-go-go-related gene (hERG) not only encodes a potassium-selective voltage-gated ion channel essential for normal electrical activity in the heart but is also a major drug anti-target. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome, which predisposes individuals to potentially deadly arrhythmias. However, not all hERG-blocking drugs are proarrhythmic, and their differential affinities to discrete channel conformational states have been suggested to contribute to arrhythmogenicity. We used Rosetta electron density refinement and homology modeling to build structur...
Source: Frontiers in Pharmacology - November 14, 2023 Category: Drugs & Pharmacology Source Type: research
Studying Long QT Syndrome Caused by < em > NAA10 < /em > Genetic Variants Using Patient-Derived Induced Pluripotent Stem Cells
Circulation. 2023 Nov 14;148(20):1598-1601. doi: 10.1161/CIRCULATIONAHA.122.061864. Epub 2023 Nov 13.NO ABSTRACTPMID:37956223 | DOI:10.1161/CIRCULATIONAHA.122.061864 (Source: Circulation)
Source: Circulation - November 13, 2023 Category: Cardiology Authors: Nadjet Belbachir Yiyang Wu Mengcheng Shen Sophia L Zhang Joe Z Zhang Chun Liu Bjorn C Knollmann Gholson J Lyon Ning Ma Joseph C Wu Source Type: research
Type 3 long QT syndrome: is the effectiveness of treatment with beta-blockers population-specific?
Efficacy of beta blocker treatment in type 3 long QT syndrome (LQT3) remains debated. (Source: Heart Rhythm)
Source: Heart Rhythm - November 11, 2023 Category: Cardiology Authors: Alexis Hermida, Jean-Baptiste Gourraud, Isabelle Denjoy, V éronique Fressart, Florence Kyndt, Alice Maltret, Diala Khraiche, Didier Klug, Philippe Mabo, Frédéric Sacher, Philippe Maury, Pierre Winum, Pascal Defaye, Gael Clerici, Dominique Babuty, Yedid Source Type: research
Proof-of-concept for monoclonal antibody therapy in a cellular model of acquired long QT syndrome type 3
Am J Physiol Heart Circ Physiol. 2023 Nov 10. doi: 10.1152/ajpheart.00628.2023. Online ahead of print.ABSTRACTLong QT syndrome (LQTS) type 3 although less common than the first two forms, differs in that arrhythmic events are less likely triggered by adrenergic stimuli and are more often lethal. Effective pharmacological treatment is challenged by inter-individual differences, mutation dependence and adverse effects, translating into an increased use of invasive measures (implantable cardioverter-defibrillator, sympathetic denervation) in LQTS type 3 patients. Previous studies have demonstrated the therapeutic potential of...
Source: American Journal of Physiology. Heart and Circulatory Physiology - November 10, 2023 Category: Physiology Authors: Lenke Kis Jin Li Source Type: research
Proof-of-concept for monoclonal antibody therapy in a cellular model of acquired long QT syndrome type 3
Am J Physiol Heart Circ Physiol. 2023 Nov 10. doi: 10.1152/ajpheart.00628.2023. Online ahead of print.ABSTRACTLong QT syndrome (LQTS) type 3 although less common than the first two forms, differs in that arrhythmic events are less likely triggered by adrenergic stimuli and are more often lethal. Effective pharmacological treatment is challenged by inter-individual differences, mutation dependence and adverse effects, translating into an increased use of invasive measures (implantable cardioverter-defibrillator, sympathetic denervation) in LQTS type 3 patients. Previous studies have demonstrated the therapeutic potential of...
Source: American Journal of Physiology. Heart and Circulatory Physiology - November 10, 2023 Category: Physiology Authors: Lenke Kis Jin Li Source Type: research
Proof-of-concept for monoclonal antibody therapy in a cellular model of acquired long QT syndrome type 3
Am J Physiol Heart Circ Physiol. 2023 Nov 10. doi: 10.1152/ajpheart.00628.2023. Online ahead of print.ABSTRACTLong QT syndrome (LQTS) type 3 although less common than the first two forms, differs in that arrhythmic events are less likely triggered by adrenergic stimuli and are more often lethal. Effective pharmacological treatment is challenged by inter-individual differences, mutation dependence and adverse effects, translating into an increased use of invasive measures (implantable cardioverter-defibrillator, sympathetic denervation) in LQTS type 3 patients. Previous studies have demonstrated the therapeutic potential of...
Source: American Journal of Physiology. Heart and Circulatory Physiology - November 10, 2023 Category: Physiology Authors: Lenke Kis Jin Li Source Type: research
Proof-of-concept for monoclonal antibody therapy in a cellular model of acquired long QT syndrome type 3
Am J Physiol Heart Circ Physiol. 2023 Nov 10. doi: 10.1152/ajpheart.00628.2023. Online ahead of print.ABSTRACTLong QT syndrome (LQTS) type 3 although less common than the first two forms, differs in that arrhythmic events are less likely triggered by adrenergic stimuli and are more often lethal. Effective pharmacological treatment is challenged by inter-individual differences, mutation dependence and adverse effects, translating into an increased use of invasive measures (implantable cardioverter-defibrillator, sympathetic denervation) in LQTS type 3 patients. Previous studies have demonstrated the therapeutic potential of...
Source: American Journal of Physiology. Heart and Circulatory Physiology - November 10, 2023 Category: Physiology Authors: Lenke Kis Jin Li Source Type: research
Proof-of-concept for monoclonal antibody therapy in a cellular model of acquired long QT syndrome type 3
Am J Physiol Heart Circ Physiol. 2023 Nov 10. doi: 10.1152/ajpheart.00628.2023. Online ahead of print.ABSTRACTLong QT syndrome (LQTS) type 3 although less common than the first two forms, differs in that arrhythmic events are less likely triggered by adrenergic stimuli and are more often lethal. Effective pharmacological treatment is challenged by inter-individual differences, mutation dependence and adverse effects, translating into an increased use of invasive measures (implantable cardioverter-defibrillator, sympathetic denervation) in LQTS type 3 patients. Previous studies have demonstrated the therapeutic potential of...
Source: American Journal of Physiology. Heart and Circulatory Physiology - November 10, 2023 Category: Physiology Authors: Lenke Kis Jin Li Source Type: research
