Evidence for functional expression of TRPM7 channels in human atrial myocytes.
Transient receptor potential melastatin-7 (TRPM7) channels have been recently reported in human atrial fibroblasts and are believed to mediate fibrogenesis in human atrial fibrillation. The present study investigates whether TRPM7 channels are expressed in human atrial myocytes using whole-cell patch voltage-clamp, RT-PCR and Western blotting analysis. It was found that a gradually activated TRPM7-like current was recorded with a K(+)- and Mg(2+)-free pipette solution in human atrial myocytes. The current was enhanced by removing extracellular Ca(2+) and Mg(2+), and the current increase could be inhibited by Ni(2+) or Ba(2+). The TRPM7-like current was potentiated by acidic pH and inhibited by La(3+) and 2-aminoethoxydiphenyl borate. In addition, Ca(2+)-activated TRPM4-like current was recorded in human atrial myocytes with the addition of the Ca(2+) ionophore A23187 in bath solution. RT-PCR and Western immunoblot analysis revealed that in addition to TRPM4, TRPM7 channel current, mRNA and protein expression were evident in human atrial myocytes. Interestingly, TRPM7 channel protein, but not TRPM4 channel protein, was significantly increased in human atrial specimens from the patients with atrial fibrillation. Our results demonstrate for the first time that functional TRPM7 channels are present in human atrial myocytes, and the channel expression is upregulated in the atria with atrial fibrillation.
Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Yan-Hui
YH
Zhang
Hai-Ying
HY
Sun
Kui-Hao
KH
Chen
Xin-Ling
XL
Du
Bo
B
Liu
Lik-Cheung
LC
Cheng
Xin
X
Li
Man-Wen
MW
Jin
Gui-Rong
GR
Li
D001281:Atrial Fibrillation / Q000378:metabolism; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D028581:Lanthanoid Series Elements / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000502:physiology*
D001896:Boron Compounds; D028581:Lanthanoid Series Elements; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; C109986:2-aminoethoxydiphenyl borate; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D008274:Magnesium; D002118:Calcium