Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current
| dc.contributor.author | Gwanyanya, Asfree | |
| dc.contributor.author | Andriulė, Inga | |
| dc.contributor.author | Istrate, Bogdan M. | |
| dc.contributor.author | Easmin, Farjana | |
| dc.contributor.author | Mubagwa, Kanigula | |
| dc.contributor.author | Mačianskienė, Regina | |
| dc.date.accessioned | 2021-10-06T12:02:00Z | |
| dc.date.available | 2021-10-06T12:02:00Z | |
| dc.date.issued | 2021-08-14 | |
| dc.date.updated | 2021-08-26T13:27:55Z | |
| dc.description.abstract | 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. | |
| dc.identifier | doi: 10.3390/ijms22168744 | |
| dc.identifier.apacitation | Gwanyanya, A., Andriulė, I., Istrate, Bogdan M., Easmin, F., Mubagwa, K., & Mačianskienė, R. (2021). Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current. http://hdl.handle.net/11427/34098 | en_ZA |
| dc.identifier.chicagocitation | Gwanyanya, Asfree, Inga Andriulė, Bogdan M. Istrate, Farjana Easmin, Kanigula Mubagwa, and Regina Mačianskienė "Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current." (2021) http://hdl.handle.net/11427/34098 | en_ZA |
| dc.identifier.citation | International Journal of Molecular Sciences 22 (16): 8744 (2021) | |
| dc.identifier.ris | TY - Journal Article AU - Gwanyanya, Asfree AU - Andriulė, Inga AU - Istrate, Bogdan M. AU - Easmin, Farjana AU - Mubagwa, Kanigula AU - Mačianskienė, Regina AB - 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. DA - 2021-08-14 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PY - 2021 T1 - Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current TI - Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current UR - http://hdl.handle.net/11427/34098 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/34098 | |
| dc.identifier.vancouvercitation | Gwanyanya A, Andriulė I, Istrate Bogdan M, Easmin F, Mubagwa K, Mačianskienė R. Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current. 2021; http://hdl.handle.net/11427/34098. | en_ZA |
| dc.publisher | Multidisciplinary Digital Publishing Institute | |
| dc.title | Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current | |
| dc.type | Journal Article |