Calcium Signaling

The main mechanisms for elevating intracellular Ca²⁺ involve:

1. Calcium entry through voltage- or ligand-gated calcium channels in the plasma membrane
2. Ryanodine receptor- and IP₃ receptor-mediated calcium release from the sarcoplasmic reticulum
3. Na⁺/Ca²⁺ exchange in the mitochondrial membrane

The main mechanisms for removing calcium from the cytoplasm involve:

1. Ca²⁺ ATPase in the plasma membrane
2. Na⁺/Ca²⁺ exchange in the plasma membrane

The diagram below summarizes the main cellular Ca²⁺ transport pathways, and some examples of the key sites for pharmacological manipulation.

The Major Cellular Ca²⁺ Transport Pathways

Ca²⁺ movements are highlighted in orange, while the gradients and stimuli that drive Ca²⁺ movement are indicated in blue text. Pharmacological agents are indicated in green text. The lefthand side of the diagram illustrates the processes that decrease [Ca²⁺]_i, while the righthand side shows pathways that elevate cytosolic Ca²⁺. The elongated ellipses represent endoplasmic reticulum; the short ellipses represent mitochondria. Abbreviations include: cADPR - cyclic ADP ribose, I_crac - the capacitative calcium entry current; L/VGCC - ligand/voltage gated calcium channel.