Detection of TRPM6 and TRPM7 Proteins in Normal and Diseased Cardiac Atrial Tissue and Isolated Cardiomyocytes

Int J Mol Sci. 2022 Nov 28;23(23):14860. doi: 10.3390/ijms232314860.

Abstract

Magnesium-sensitive transient receptor potential melastatin (TRPM) ion channels, TRPM6 and TRPM7, are present in several organs, but their roles in the heart remain unclear. Therefore, here, we studied the expression patterns of TRPM6 and TRPM7 in normal and diseased myocardium. Cardiac atrial tissue and cardiomyocytes were obtained from healthy pigs and undiseased human hearts as well as from hearts of patients with ischemic heart disease (IHD) or atrial fibrillation (AF). Immunofluorescence and ELISA were used to detect TRP proteins. TRPM6 and TRPM7 immunofluorescence signals, localized at/near the cell surface or intracellularly, were detected in pig and human atrial tissues. The TRP channel modulators carvacrol (CAR, 100 µM) or 2-aminoethoxydiphenyl borate (2-APB, 500 µM) decreased the TRPM7 signal, but enhanced that of TRPM6. At a higher concentration (2 mM), 2-APB enhanced the signals of both proteins. TRPM6 and TRPM7 immunofluorescence signals and protein concentrations were increased in atrial cells and tissues from IHD or AF patients. TRPM6 and TRPM7 proteins were both detected in cardiac atrial tissue, with relatively similar subcellular localization, but distinctive drug sensitivity profiles. Their upregulated expression in IHD and AF suggests a possible role of the channels in cardiac atrial disease.

Keywords: TRPM6 and TRPM7 channels; atrial fibrillation; atrial myocyte and tissue; ischemic heart disease.

MeSH terms

  • Animals
  • Atrial Fibrillation* / metabolism
  • Cell Membrane / metabolism
  • Heart Atria / metabolism
  • Humans
  • Magnesium / metabolism
  • Myocytes, Cardiac / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Swine
  • TRPM Cation Channels* / genetics
  • TRPM Cation Channels* / metabolism

Substances

  • TRPM Cation Channels
  • Magnesium
  • TRPM6 protein, human
  • TRPM7 protein, human
  • Protein Serine-Threonine Kinases

Grants and funding

This research received no external funding. K.M. was supported by funding from VLIR-UOS in the frame of an Institutional University Cooperation between Flemish universities and the Université Catholique de Bukavu.