Suppression of TRPC3 Leads to Disappearance of Store-operated Channels and Formation of a New Type of Store-independent Channels in A431 Cells

In most non-excitable cells, calcium (Ca2+) release from the inositol 1,4,5-trisphosphate (InsP(3))-sensitive intracellular Ca2+ stores is coupled to Ca2+ influx through the plasma membrane Ca2+ channels whose molecular composition is poorly understood. Several members of mammalian TRP-related protein family have been implicated to both receptor- and store-operated Ca2+ influx. Here we investigated the role of the native transient receptor potential 3(TRPC3) homologue in mediating the store- and receptor- operated calcium entry in A431 cells. We show that suppression of TRPC3 protein levels by small interfering RNA ( siRNA) leads to a significant reduction in store- operated calcium influx without affecting the receptoroperated calcium influx. With single-channel analysis, we further demonstrate that reduction of TRPC3 levels results in suppression of specific subtype of store- operated calcium channels and activation of store- independent channels. Our data suggest that TRPC3 is required for the formation of functional store-operated channels in A431 cells.