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The ubiquitous transient receptor potential canonical (TRPC) channels function as non-selective, Ca2+-permeable channels and mediate numerous cellular functions.It is commonly assumed that TRPC channels are activated by stimulation of Gαq-PLC-coupled receptors.However, whether the Gαtq-PLC pathway is the main regulator of TRPC4/5 channels and how other Gα proteins may regulate these channels are poorly understood.