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

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...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-08, Vol.22 (16), p.8744
Main Authors: Gwanyanya, Asfree, Andriulė, Inga, Istrate, Bogdan M., Easmin, Farjana, Mubagwa, Kanigula, Mačianskienė, Regina
Format: Article
Language:English
Subjects:
Action potential
Calcium channels (L-type)
Calcium ions
cardiac
Cardiomyocytes
Channels
Depolarization
Dialysis
Divalent cations
Heart
Homeostasis
Immunofluorescence
ion channel
Magnesium
Myocytes
Pacemakers
Physiological effects
Physiology
Protein expression
Proteins
Transient receptor potential proteins
TRPM6
TRPM7
Ventricle
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22168744