Proposed signal pathway coupling store depletion to activation of TRPC1 channels. A, B) Traces show that bath application of noradrenaline evoked TRPC1 channel activity in a concentration-dependent manner in cell-attached patches held at −80 mV, which were greatly reduced in VSMCs expressing PLCβ1 shRNA (B) compared to scrambled shRNA (A). C) Mean data show the inhibitory effect of PLCβ1 shRNA on noradrenaline-induced TRPC1 channel activity (n = 7). **P < 0.01; ***P < 0.001. D) Proposed activation model of TRPC1 channels in VSMCs. In the closed state, TRPC1 does not interact with Gαq and PLCβ1. Following Ca2+ store depletion, TRPC1 forms complexes with Gαq and PLCβ1 to cause PIP2 hydrolysis and formation of DAG, which stimulates PKC activity, phosphorylation of TRPC1 subunits, and channel opening.