Calcium Signaling/Calcium Metabolism

The divalent cation calcium (Ca2+) is used by cells as a second messenger to control many cellular processes including muscle contraction, secretion, metabolism, neuronal excitability, cell proliferation, and cell death. The cell has access to two sources of signal Ca2+, entry from the external medium and release from internal stores. These Ca2+ ON mechanisms are balanced by Ca2+pumps which constitute the OFF mechanisms responsible for removing the Ca2+ signal. These ON and OFF mechanisms are often organized to produce brief spikes and waves of calcium. Cells may avoid the cytotoxic effects of calcium by employing this oscillatory mode of calcium signaling.

Signaling Functions of Calcium
Calcium functions as a second messenger to regulate a great variety of cellular processes.
Contraction: Excitation-contraction coupling in skeletal and cardiac muscle depends upon the release of calcium by RYRs located on the sarcoplasmic reticulum. Pharmacomechanical coupling in smooth muscle is controlled by the release of calcium from either InsP3Rs or RYRs depending on the muscle type.
Secretion: During stimulus-secretion coupling, calcium acts either to release preformed materials by exocytosis (e.g. transmitter release at synaptic endings) or to stimulate the ionic mechanisms responsible for fluid secretion (e.g. in exocrine glands).
Metabolism: Glycogen breakdown in liver cells is controlled by a calcium-dependent activation of phosphorylase.
Neuronal excitability: The excitability of neurons can be modulated through calcium-dependent effects on ion channels (e.g. potassium channels) and ionotropic receptors (e.g. AMPA receptors). Some of these effects of calcium are long lasting, such as long-term potentiation (LTP) or long-term depression (LTD), and have been implicated in learning and memory.
Cell proliferation: Calcium plays an important role both in fertilization and in controlling cell proliferation. In the case of lymphocyte activation, the immunosuppressant drug cyclosporin A acts by inhibiting the calcium-dependent transfer of information from the T cell receptor to the nucleus.
Cell death: Elevated levels of calcium, especially if maintained for long periods, can be cytotoxic. Calcium has been implicated in both necrosis and apoptosis.