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Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells

BACKGROUND: Purkinje cells (PCs) are important in cardiac arrhythmogenesis. Whether small‐conductance calcium‐activated potassium (SK) channels are present in PCs remains unclear. We tested the hypotheses that subtype 2 SK (SK2) channel proteins and apamin‐sensitive SK currents are abundantly presen...

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Autores principales: Reher, Thomas A., Wang, Zhuo, Hsueh, Chia‐Hsiang, Chang, Po‐Cheng, Pan, Zhenwei, Kumar, Mohineesh, Patel, Jheel, Tan, Jian, Shen, Changyu, Chen, Zhenhui, Fishbein, Michael C., Rubart, Michael, Boyden, Penelope, Chen, Peng‐Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669169/
https://www.ncbi.nlm.nih.gov/pubmed/28550095
http://dx.doi.org/10.1161/JAHA.117.005471
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author Reher, Thomas A.
Wang, Zhuo
Hsueh, Chia‐Hsiang
Chang, Po‐Cheng
Pan, Zhenwei
Kumar, Mohineesh
Patel, Jheel
Tan, Jian
Shen, Changyu
Chen, Zhenhui
Fishbein, Michael C.
Rubart, Michael
Boyden, Penelope
Chen, Peng‐Sheng
author_facet Reher, Thomas A.
Wang, Zhuo
Hsueh, Chia‐Hsiang
Chang, Po‐Cheng
Pan, Zhenwei
Kumar, Mohineesh
Patel, Jheel
Tan, Jian
Shen, Changyu
Chen, Zhenhui
Fishbein, Michael C.
Rubart, Michael
Boyden, Penelope
Chen, Peng‐Sheng
author_sort Reher, Thomas A.
collection PubMed
description BACKGROUND: Purkinje cells (PCs) are important in cardiac arrhythmogenesis. Whether small‐conductance calcium‐activated potassium (SK) channels are present in PCs remains unclear. We tested the hypotheses that subtype 2 SK (SK2) channel proteins and apamin‐sensitive SK currents are abundantly present in PCs. METHODS AND RESULTS: We studied 25 normal rabbit ventricles, including 13 patch‐clamp studies, 4 for Western blotting, and 8 for immunohistochemical staining. Transmembrane action potentials were recorded in current‐clamp mode using the perforated‐patch technique. For PCs, the apamin (100 nmol/L) significantly prolonged action potential duration measured to 80% repolarization by an average of 10.4 ms (95% CI, 0.11–20.72) (n=9, P=0.047). Voltage‐clamp study showed that apamin‐sensitive SK current density was significantly larger in PCs compared with ventricular myocytes at potentials ≥0 mV. Western blotting of SK2 expression showed that the SK2 protein expression in the midmyocardium was 58% (P=0.028) and the epicardium was 50% (P=0.018) of that in the pseudotendons. Immunostaining of SK2 protein showed that PCs stained stronger than ventricular myocytes. Confocal microscope study showed SK2 protein was distributed to the periphery of the PCs. CONCLUSIONS: SK2 proteins are more abundantly present in the PCs than in the ventricular myocytes of normal rabbit ventricles. Apamin‐sensitive SK current is important in ventricular repolarization of normal PCs.
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spelling pubmed-56691692017-11-09 Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells Reher, Thomas A. Wang, Zhuo Hsueh, Chia‐Hsiang Chang, Po‐Cheng Pan, Zhenwei Kumar, Mohineesh Patel, Jheel Tan, Jian Shen, Changyu Chen, Zhenhui Fishbein, Michael C. Rubart, Michael Boyden, Penelope Chen, Peng‐Sheng J Am Heart Assoc Original Research BACKGROUND: Purkinje cells (PCs) are important in cardiac arrhythmogenesis. Whether small‐conductance calcium‐activated potassium (SK) channels are present in PCs remains unclear. We tested the hypotheses that subtype 2 SK (SK2) channel proteins and apamin‐sensitive SK currents are abundantly present in PCs. METHODS AND RESULTS: We studied 25 normal rabbit ventricles, including 13 patch‐clamp studies, 4 for Western blotting, and 8 for immunohistochemical staining. Transmembrane action potentials were recorded in current‐clamp mode using the perforated‐patch technique. For PCs, the apamin (100 nmol/L) significantly prolonged action potential duration measured to 80% repolarization by an average of 10.4 ms (95% CI, 0.11–20.72) (n=9, P=0.047). Voltage‐clamp study showed that apamin‐sensitive SK current density was significantly larger in PCs compared with ventricular myocytes at potentials ≥0 mV. Western blotting of SK2 expression showed that the SK2 protein expression in the midmyocardium was 58% (P=0.028) and the epicardium was 50% (P=0.018) of that in the pseudotendons. Immunostaining of SK2 protein showed that PCs stained stronger than ventricular myocytes. Confocal microscope study showed SK2 protein was distributed to the periphery of the PCs. CONCLUSIONS: SK2 proteins are more abundantly present in the PCs than in the ventricular myocytes of normal rabbit ventricles. Apamin‐sensitive SK current is important in ventricular repolarization of normal PCs. John Wiley and Sons Inc. 2017-05-26 /pmc/articles/PMC5669169/ /pubmed/28550095 http://dx.doi.org/10.1161/JAHA.117.005471 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Reher, Thomas A.
Wang, Zhuo
Hsueh, Chia‐Hsiang
Chang, Po‐Cheng
Pan, Zhenwei
Kumar, Mohineesh
Patel, Jheel
Tan, Jian
Shen, Changyu
Chen, Zhenhui
Fishbein, Michael C.
Rubart, Michael
Boyden, Penelope
Chen, Peng‐Sheng
Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells
title Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells
title_full Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells
title_fullStr Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells
title_full_unstemmed Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells
title_short Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells
title_sort small‐conductance calcium‐activated potassium current in normal rabbit cardiac purkinje cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669169/
https://www.ncbi.nlm.nih.gov/pubmed/28550095
http://dx.doi.org/10.1161/JAHA.117.005471
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