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

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

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