Fig. 2.

Regulation of [Ca²⁺]_i and Ca²⁺-dependent cellular response. During cell activation, Ca²⁺ is released from the intracellular stores through IP₃-sensitive Ca²⁺ channels and the ryanodine-sensitive Ca²⁺-induced Ca²⁺ release mechanism. Extracellular Ca²⁺ enters the cell through voltage-gated, ligand-gated, store-operated, and nonspecific channels. The increased [Ca²⁺]_i triggers specific responses in red blood cells, platelets, immune cells, endothelial cells, and VSM cells. When the cell stimulus is removed, [Ca²⁺]_i returns back to normal level via the Ca²⁺-ATPase pump and Na/Ca exchanger. Also, the Na/K-pump and Na/H exchanger could affect the membrane potential and intracellular pH and further modify the Ca²⁺ response. Extremely high levels of [Ca²⁺]_i are taken up by the mitochondria.