Calcium Signaling

Calcium functions as a second messenger and is involved in the regulation of a multitude of cellular physiological processes.


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

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, Icrac - the capacitative calcium entry current; L/VGCC - ligand/voltage gated calcium channel.