Background: A new super-family of channels that may have a role in cardiac calcium homeostasis has recently been described. These are non-selective and non-voltage-gated transient receptor potential (TRP) channels; most of them are permeable for Ca2+ and gated by diverse stimuli. We have previously shown that the expression level of one of which, TRPV2, is exclusively upregulated in the heart 3-5 days post myocardial infarction compared to sham-operated animals. We sought to assess whether TRPV2 overexpression may affect cardiomyocyte cell viability following myocardial infarction.
Methods: Murine HL-1 cardiac cells were exposed to hypoxic conditions for 18 hours. TRPV2 levels on the outer cell membrane were tested by flow cytometry using an anti- TRPV2 antibody. Cellular viability was assessed by Annexin-FITC-PI assay followed by flow cytometry analysis. The direct effect of TRPV2 on cell viability was studied by introducing a TRPV2 or scramble siRNA to the cells prior to the exposure to hypoxia.
Results: TRPV2 expression on the cell membrane was elevated by 60% upon exposure to hypoxia. The upregulation of this channel protein was correlated with a significant reduction in cellular viability (77.8± 3.1 versus 58.9± 4.3 percent viability in normoxic versus hypoxic cells). Interestingly, transient transfection with a TRPV2 siRNA inhibited the cell death observed in the hypoxic scramble- siRNA or untransfected HL-1 cells. The viability of HL-1 cells grown under normoxic conditions was not affected by the siRNA.
Conclusion: TRPV2 may play an important role in mediating cardiomyocyte cell death following myocardial infacrion. These data point to a potential novel therapeutic target for cardiomyocye cell loss occurring shortly after an acute MI.
