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Published on: August 11, 2010
No functional TRPA1 in cardiomyocytes
Clara Hoebart1, Natalia S Rojas-Galvan1, Cosmin I Ciotu1
1Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Insights
The transient receptor potential ankyrin 1 (TRPA1) channel is not directly expressed in cardiomyocytes, despite evidence of its role in heart function. This study found no significant TRPA1 activity or expression in cardiac cells, suggesting its cardiac effects are indirect.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Ion Channel Research
Background:
- Growing evidence suggests the transient receptor potential ankyrin 1 (TRPA1) channel influences cardiac physiology and pathophysiology.
- The precise location and function of TRPA1 within the heart, particularly in cardiomyocytes, remain unclear.
Purpose of the Study:
- To investigate the expression site of TRPA1 in the heart.
- To determine if TRPA1 channels are present and functional within cardiomyocytes.
Main Methods:
- Microfluorimetry was used to detect calcium changes in primary mouse cardiomyocytes and H9c2/HL-1 cell lines.
- TRPA1 mRNA levels were quantified in mouse and human cardiac tissues and cells using RT-qPCR.
- Dorsal root ganglia served as positive controls for TRPA1 expression and function.
Main Results:
- Specific TRPA1 agonists (JT010, PF-4840154) did not elicit a response in native or electrically paced cardiomyocytes or cardiac cell lines.
- Marginal TRPA1 mRNA levels were detected in cardiomyocytes, even under conditions mimicking pathophysiology.
- TRPA1 mRNA levels in human heart samples were significantly lower than in dorsal root ganglia.
Conclusions:
- TRPA1 is not directly expressed or functionally active in cardiomyocytes.
- The observed role of TRPA1 in cardiac pathophysiology is likely mediated through indirect mechanisms rather than direct action on cardiac cells.
Aim:
There is mounting evidence that TRPA1 has a role in cardiac physiology and pathophysiology. We aim to clarify the site of TRPA1 expression in the heart and in particular whether the channel is expressed in cardiomyocytes.
Methods:
Due to the high calcium conductance of TRPA1, and marginal calcium changes being detectable, microfluorimetry in primary mouse cardiomyocytes, and in the cardiomyocyte cell lines H9c2 and HL-1, was applied. TRPA1 mRNA in mouse and human hearts, primary cardiomyocytes, and the cardiac cell lines were quantified. Dorsal root ganglia served as control for both methods.
Results:
In addition to AITC, the more potent and specific TRPA1 agonists JT010 and PF-4840154 failed to elicit a TRPA1-mediated response in native and electrically paced primary cardiomyocytes, and the cardiomyocyte cell lines H9c2 and HL-1. There were only marginal levels of TRPA1 mRNA in cardiomyocytes and cardiac cell lines, also in conditions of cell differentiation or inflammation, which might occur in pathophysiological conditions. Similarly, TRPV1 agonist capsaicin did not activate primary mouse cardiomyocytes, did not alter electrically paced activity in these, and did not activate H9c2 cells or alter spontaneous activity of HL-1 cells. Human pluripotent stem cells differentiated to cardiomyocytes had no relevant TRPA1 mRNA levels. Also in human post-mortem heart samples, TRPA1 mRNA levels were substantially lower compared with the respective dorsal root ganglion.
Conclusion:
The results do not question a role of TRPA1 in the heart but exclude a direct effect in cardiomyocytes.
