Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current
The cardiac Mg<sup>2+</sup>-sensitive, TRPM6, and TRPM7-like channels remain undefined, especially with the uncertainty regarding TRPM6 expression in cardiomyocytes. Additionally, their contribution to the cardiac action potential (AP) profile is unclear. Immunofluorescence assays showed...
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2021-08-01
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author | Asfree Gwanyanya Inga Andriulė Bogdan M. Istrate Farjana Easmin Kanigula Mubagwa Regina Mačianskienė |
author_facet | Asfree Gwanyanya Inga Andriulė Bogdan M. Istrate Farjana Easmin Kanigula Mubagwa Regina Mačianskienė |
author_sort | Asfree Gwanyanya |
collection | DOAJ |
description | The cardiac Mg<sup>2+</sup>-sensitive, TRPM6, and TRPM7-like channels remain undefined, especially with the uncertainty regarding TRPM6 expression in cardiomyocytes. Additionally, their contribution to the cardiac action potential (AP) profile is unclear. Immunofluorescence assays showed the expression of the TRPM6 and TRPM7 proteins in isolated pig atrial and ventricular cardiomyocytes, of which the expression was modulated by incubation in extracellular divalent cation-free conditions. In patch clamp studies of cells dialyzed with solutions containing zero intracellular Mg<sup>2+</sup> concentration ([Mg<sup>2+</sup>]<sub>i</sub>) to activate the Mg<sup>2+</sup>-sensitive channels, raising extracellular [Mg<sup>2+</sup>] ([Mg<sup>2+</sup>]<sub>o</sub>) from the 0.9-mM baseline to 7.2 mM prolonged the AP duration (APD). In contrast, no such effect was observed in cells dialyzed with physiological [Mg<sup>2+</sup>]<sub>i</sub>. Under voltage clamp, in cells dialyzed with zero [Mg<sup>2+</sup>]<sub>i</sub>, depolarizing ramps induced an outward-rectifying current, which was suppressed by raising [Mg<sup>2+</sup>]<sub>o</sub> and was absent in cells dialyzed with physiological [Mg<sup>2+</sup>]<sub>i</sub>. In cells dialyzed with physiological [Mg<sup>2+</sup>]<sub>i</sub>, raising [Mg<sup>2+</sup>]<sub>o</sub> decreased the L-type Ca<sup>2+</sup> current and the total delayed-rectifier current but had no effect on the APD. These results suggest a co-expression of the TRPM6 and TRPM7 proteins in cardiomyocytes, which are therefore the molecular candidates for the native cardiac Mg<sup>2+</sup>-sensitive channels, and also suggest that the cardiac Mg<sup>2+</sup>-sensitive current shortens the APD, with potential implications in arrhythmogenesis. |
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spelling | doaj.art-b8e0ef62e46246888418c9abed669de42023-11-22T07:59:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216874410.3390/ijms22168744Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like CurrentAsfree Gwanyanya0Inga Andriulė1Bogdan M. Istrate2Farjana Easmin3Kanigula Mubagwa4Regina Mačianskienė5Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, BelgiumInstitute of Cardiology, Lithuanian University of Health Sciences, 50103 Kaunas, LithuaniaDepartment of Cardiovascular Sciences, KU Leuven, 3000 Leuven, BelgiumDepartment of Cardiovascular Sciences, KU Leuven, 3000 Leuven, BelgiumDepartment of Cardiovascular Sciences, KU Leuven, 3000 Leuven, BelgiumInstitute of Cardiology, Lithuanian University of Health Sciences, 50103 Kaunas, LithuaniaThe cardiac Mg<sup>2+</sup>-sensitive, TRPM6, and TRPM7-like channels remain undefined, especially with the uncertainty regarding TRPM6 expression in cardiomyocytes. Additionally, their contribution to the cardiac action potential (AP) profile is unclear. Immunofluorescence assays showed the expression of the TRPM6 and TRPM7 proteins in isolated pig atrial and ventricular cardiomyocytes, of which the expression was modulated by incubation in extracellular divalent cation-free conditions. In patch clamp studies of cells dialyzed with solutions containing zero intracellular Mg<sup>2+</sup> concentration ([Mg<sup>2+</sup>]<sub>i</sub>) to activate the Mg<sup>2+</sup>-sensitive channels, raising extracellular [Mg<sup>2+</sup>] ([Mg<sup>2+</sup>]<sub>o</sub>) from the 0.9-mM baseline to 7.2 mM prolonged the AP duration (APD). In contrast, no such effect was observed in cells dialyzed with physiological [Mg<sup>2+</sup>]<sub>i</sub>. Under voltage clamp, in cells dialyzed with zero [Mg<sup>2+</sup>]<sub>i</sub>, depolarizing ramps induced an outward-rectifying current, which was suppressed by raising [Mg<sup>2+</sup>]<sub>o</sub> and was absent in cells dialyzed with physiological [Mg<sup>2+</sup>]<sub>i</sub>. In cells dialyzed with physiological [Mg<sup>2+</sup>]<sub>i</sub>, raising [Mg<sup>2+</sup>]<sub>o</sub> decreased the L-type Ca<sup>2+</sup> current and the total delayed-rectifier current but had no effect on the APD. These results suggest a co-expression of the TRPM6 and TRPM7 proteins in cardiomyocytes, which are therefore the molecular candidates for the native cardiac Mg<sup>2+</sup>-sensitive channels, and also suggest that the cardiac Mg<sup>2+</sup>-sensitive current shortens the APD, with potential implications in arrhythmogenesis.https://www.mdpi.com/1422-0067/22/16/8744TRPM6TRPM7ion channelaction potentialcardiacmagnesium |
spellingShingle | Asfree Gwanyanya Inga Andriulė Bogdan M. Istrate Farjana Easmin Kanigula Mubagwa Regina Mačianskienė Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current International Journal of Molecular Sciences TRPM6 TRPM7 ion channel action potential cardiac magnesium |
title | Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current |
title_full | Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current |
title_fullStr | Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current |
title_full_unstemmed | Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current |
title_short | Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current |
title_sort | modulation of the cardiac myocyte action potential by the magnesium sensitive trpm6 and trpm7 like current |
topic | TRPM6 TRPM7 ion channel action potential cardiac magnesium |
url | https://www.mdpi.com/1422-0067/22/16/8744 |
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