A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart disease
The hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) gene has been reported to regulate the spontaneous depolarization of sinoatrial node cells. A novel HCN4 mutation (c.2036 G>A) may lead to sick sinus syndrome. The green fluorescent protein (GFP) and either the wil...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Channels |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19336950.2025.2517851 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839639388161572864 |
|---|---|
| author | Fengxiao Zhang Ning Zhao Lin Wang Hua Peng Ying Jiang Min Cheng Feng Zhu |
| author_facet | Fengxiao Zhang Ning Zhao Lin Wang Hua Peng Ying Jiang Min Cheng Feng Zhu |
| author_sort | Fengxiao Zhang |
| collection | DOAJ |
| description | The hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) gene has been reported to regulate the spontaneous depolarization of sinoatrial node cells. A novel HCN4 mutation (c.2036 G>A) may lead to sick sinus syndrome. The green fluorescent protein (GFP) and either the wild-type (WT) or C679Y mutant (mut) were co-transfected into HEK293 cells to investigate the impact of the mutation on HCN4 channel function. The whole-cell patch-clamp approach was utilized to record HCN4 currents. According to electrophysiological recording, the current amplitude and density generated by mut-C679Y HCN4 channels were much lower than those generated by WT channels. HCN4 channel current activation was not significantly affected by the C679Y mutation. Because of the little current, analyzing the mut channel deactivation kinetic was challenging. Thus, we have identified a novel HCN4 gene mutation that is connected to bradycardia, left ventricular noncompaction, and diverse valve-related heart conditions. |
| format | Article |
| id | doaj-art-d95b664c067f4439ad4e06ed6e9d2495 |
| institution | Matheson Library |
| issn | 1933-6950 1933-6969 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Channels |
| spelling | doaj-art-d95b664c067f4439ad4e06ed6e9d24952025-07-04T10:05:18ZengTaylor & Francis GroupChannels1933-69501933-69692025-12-0119110.1080/19336950.2025.2517851A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart diseaseFengxiao Zhang0Ning Zhao1Lin Wang2Hua Peng3Ying Jiang4Min Cheng5Feng Zhu6Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaPediatric Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaPediatric Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) gene has been reported to regulate the spontaneous depolarization of sinoatrial node cells. A novel HCN4 mutation (c.2036 G>A) may lead to sick sinus syndrome. The green fluorescent protein (GFP) and either the wild-type (WT) or C679Y mutant (mut) were co-transfected into HEK293 cells to investigate the impact of the mutation on HCN4 channel function. The whole-cell patch-clamp approach was utilized to record HCN4 currents. According to electrophysiological recording, the current amplitude and density generated by mut-C679Y HCN4 channels were much lower than those generated by WT channels. HCN4 channel current activation was not significantly affected by the C679Y mutation. Because of the little current, analyzing the mut channel deactivation kinetic was challenging. Thus, we have identified a novel HCN4 gene mutation that is connected to bradycardia, left ventricular noncompaction, and diverse valve-related heart conditions.https://www.tandfonline.com/doi/10.1080/19336950.2025.2517851Sick sinus syndromeleft ventricular noncompactionHCN4 |
| spellingShingle | Fengxiao Zhang Ning Zhao Lin Wang Hua Peng Ying Jiang Min Cheng Feng Zhu A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart disease Channels Sick sinus syndrome left ventricular noncompaction HCN4 |
| title | A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart disease |
| title_full | A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart disease |
| title_fullStr | A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart disease |
| title_full_unstemmed | A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart disease |
| title_short | A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart disease |
| title_sort | rare hcn4 variant combined with sick sinus syndrome left ventricular noncompaction and complex congenital heart disease |
| topic | Sick sinus syndrome left ventricular noncompaction HCN4 |
| url | https://www.tandfonline.com/doi/10.1080/19336950.2025.2517851 |
| work_keys_str_mv | AT fengxiaozhang ararehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT ningzhao ararehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT linwang ararehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT huapeng ararehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT yingjiang ararehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT mincheng ararehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT fengzhu ararehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT fengxiaozhang rarehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT ningzhao rarehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT linwang rarehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT huapeng rarehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT yingjiang rarehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT mincheng rarehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease AT fengzhu rarehcn4variantcombinedwithsicksinussyndromeleftventricularnoncompactionandcomplexcongenitalheartdisease |