Fig. 8.

Schematics for the hypercapnic effects on TRPC channels. The TRPC channels are mostly closed at physiological pH levels. Both pH_o and pH_i are reduced with high CO₂. The low pH_o activates TRPC directly, allowing both Na⁺ and Ca²⁺ to enter the cell. The increase in intracellular Ca²⁺ concentration around the channel protein leads to further opening of TRPC5. Acidic pH_i activates TRPC5 in a Ca²⁺-dependent manner. This effect may result from Ca²⁺ release from intracellular store, Ca²⁺ dissociation from Ca²⁺-binding proteins, or the enhancement of the channel sensitivity to Ca²⁺. Open arrows indicate stimulation.