Question: 

In many cell types transient receptor potential (TRP) channels contribute to a wide array of important physiological functions but in cardiac myocytes TRPC channels are almost exclusively associated with diseases. Here, we aim to address there putative physiological, basal role.

Methods: 

We used TRPC1 and TRPC4 single KO and TRPC1/C4 double KO mice to investigate the putative physiological role of TRPC1/C4 channels in cardiac myocytes. We employed high-speed confocal microscopy, video-imaging and electrophysiology of single ventricular myocytes to investigate their subcellular as well as cellular calcium handling, contractility and electrical properties.

Results: 

In TRPC1/C4 dKO mice we found decreased global calcium transients, with both amplitude and diastolic calcium concentration affected. Myocyte contractility was reduced by more than 35%. L-type calcium current density was constant but the calcium content of the sarcoplasmic reticulum (SR) was reduced by 20%. Elementary SR-calcium release, calcium sparks, showed an almost 20% reduction in amplitude while other spatiotemporal properties were unchanged. Both Na/Ca exchanger and SR-calcium pump activity were unaltered. Using the Mn-quench approach to investigate calcium entry we found an almost 50% reduction of Mn entry into resting myocytes when comparing cells from TRPC1/C4 dKO and wt mice. Using cardiomyocytes from TRPC1 or TRPC4 single KO mice we observed a reduction of global calcium handling and SR-calcium content for both genotypes.

Conclusion: 

Both, TRPC1 and TRPC4 channels, play an important role for basal cardiac calcium handling.

(This work was supported by the DFG, BMBF and the Medical Faculty).