Transient receptor potential protein family C (TRPC) has been proposed as candidates for channels involved in capacitative calcium entry (CCE) mechanisms, but the modulation of their gene expression remains unexplored. Here we show that guinea pig gallbladder smooth muscle contains mRNA encoding TRPC1, TRPC2, TRPC3 and TRPC4 proteins whose abundance depends on [Ca²⁺ ]_i. Thus, lowering the levels of cellular calcium by the chelators EGTA and BAPTA/AM results in a down-regulation of TRPC (1-4) gene and protein expression. In contrast, activation of Ca²⁺ influx through L-type Ca²⁺ channels and Ca²⁺ release from intracellular stores induced an increase in TRPC (1-4) mRNA and protein abundance. Activation of Ca²⁺ /calmodulin-dependent kinases (CaMK) and phosphorylation of cAMP-response element binding protein (CREB) accounts for the increase in TRPC mRNA transcription in response to L-type channel mediated calcium influx . In addition to this mechanism, activation of TRPC gene expression by intracellular Ca²⁺ release also involves calcineurin pathway. According to the proposed role for these channels, activation of CCE induced an increase in TRPC1 and TRPC3 mRNA abundance, which depends on the integrity of the calcineurin and CaMK pathways. These findings show for the first time an essential auto regulatory role of Ca²⁺ in Ca²⁺ homeostasis at the level of TRPC gene and protein expression.