Mechanosensitive TRP channels in cardiovascular system

In cardiovascular system, transient receptor potential (TRP) channels may function as cellular sensors to perceive and respond to a variety of mechanical stimuli including stretch, hydrostatic pressure and flow shear force.

With the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) as models, we studied the uniaxial cyclic stretch in human cardiomyocytes. Our study demonstrated endogenous TRPV4 channels as a mechanosensor for longitudinal stretch during cardiac cycle. The channel functions to mediate cyclic stretch-induced realignment of hESC-CMs, and it also plays a key functional role in disease progression of dilated cardiomyopathy.

We also explored the molecular identity of pressure sensor in arterial baroreceptor, which serves as a frontline sensor to detect blood pressure. We identified TRPC5 channels as one mechanical sensor in the aortic and carotid baroreceptor. TRPC5 knockout mice showed diminished pressure-induced action potential firing in the afferent nerve and baroreflex-mediated heart rate reduction upon blood pressure elevation. Telemetric measurement of the daily blood pressure demonstrated that TRPC5 knockout mice displayed phenotype of severe blood pressure fluctuation. These studies suggest TRPC5 channels as a key pressure transducer in the baroreceptor.