Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current

International Journal of Molecular Sciences

Asfree Gwanyanya¹  Farjana Easmin¹  Bogdan M. Istrate¹  Kanigula Mubagwa¹  Regina Mačianskienė²  Inga Andriulė² 

[1] Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, Belgium;Institute of Cardiology, Lithuanian University of Health Sciences, 50103 Kaunas, Lithuania;

关键词: TRPM6;    TRPM7;    ion channel;    action potential;    cardiac;    magnesium;   

DOI  :  10.3390/ijms22168744

来源: DOAJ

【 摘 要 】

The cardiac Mg²⁺-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 Mg²⁺ concentration ([Mg²⁺]_i) to activate the Mg²⁺-sensitive channels, raising extracellular [Mg²⁺] ([Mg²⁺]_o) 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 [Mg²⁺]_i. Under voltage clamp, in cells dialyzed with zero [Mg²⁺]_i, depolarizing ramps induced an outward-rectifying current, which was suppressed by raising [Mg²⁺]_o and was absent in cells dialyzed with physiological [Mg²⁺]_i. In cells dialyzed with physiological [Mg²⁺]_i, raising [Mg²⁺]_o decreased the L-type Ca²⁺ 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 Mg²⁺-sensitive channels, and also suggest that the cardiac Mg²⁺-sensitive current shortens the APD, with potential implications in arrhythmogenesis.

【 授权许可】

Unknown