Hyperforin Activates Trpc6 Channels And Modulates Trpc6 And L-Type Calcium Channel Crosstalk In Cardiomyocytes

Background: Transient receptor potential ion channel-6 (TRPC6) gene expression is upregulated in cardiac remodeling. TRPC6 mediated calcium (Ca2+) entry (TMCE) in cardiomyocytes (CMs) has been classified as a source of hypertrophic signaling. Hyperforin is the active principle of St. John’s Wort extract known for antidepressant action, which demonstrated specific activation of TRPC6 channels in neurons and HEK cells. However, Hyperforin specific activation of TRPC6 channels has not been tested in CMs and its effect on the heart was unexplored. Objective: To determine a specific effect of Hyperforin on TRPC6 activation in CMs. Methods and Results: We performed 1μM-10μM Hyperforin dose response study on adult feline ventricular myocytes (AFVMs) infected with adenovirus for RFP, TRPC6 and dominant-negative (dn) TRPC6. Hyperforin dose response did not alter AFVMs survival. Measurements of TMCE showed little or no response to Hyperforin in RFP and dnTRPC6 AFVMs. However, substantial TMCE in TRPC6 AFVMs was obs...