Evidence for functional expression of TRPM7 channels in human atrial myocytes

Abstract

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 Mg2+-free pipette solution in human atrial myocytes. The current was enhanced by removing extracellular Ca2+ and Mg2+, and the current increase could be inhibited by Ni2+ or Ba2+. The TRPM7-like current was potentiated by acidic pH and inhibited by La3+ and 2-aminoethoxydiphenyl borate. In addition, Ca2+-activated TRPM4-like current was recorded in human atrial myocytes with the addition of the Ca2+ 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.

Ion channel-kinase TRPM 7 is required for maintaining cardiac automaticity

“…TRPM7 current was recently shown to be up-regulated in human atrial fibroblasts in the context of atrial fibrillation and was hypothesized to provide a Ca 2+ influx pathway inducing TGF-β1-mediated fibroblast proliferation and differentiation, thereby contributing to atrial fibrosis in the pathogenesis of atrial fibrillation (9). In addition to atrial fibroblasts, ventricular fibroblasts also have a large TRPM7 current (10), and a TRPM7-like current has been recorded from human atrial myocytes (11). Thus, TRPM7 represents a heretofore unstudied ionic current and signaling molecule in cardiac biology that may participate in arrhythmogenesis in human heart disease or contribute to normal myocardial Ca 2+ signaling.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…In adult tissues, TRPM7 may play a role as a pacemaker channel in Cajal cells and thus affect intestinal motility (Kim et al, 2011a). The channel is also present in human atrial myocytes, where its expression is upregulated during atrial fibrillation (Zhang et al, 2012c).…”

Trpm7

“…Early reports located TRPM7-like currents in pig, rat, and guinea pig ventricular myocytes (Gwanyanya et al 2004) and most recently in human atrial myocytes (Macianskiene et al 2012; Zhang et al 2012a), although the channel kinase’s role in this tissue remains to be determined. More is known about TRPM7’s function in human cardiofibroblasts, where increased TRPM7-mediated Ca influx has been linked to increased myofibroblast differentiation and fibrogenesis in patients prone to atrial fibrillation (Du et al 2010).…”