Calcium Ion as a Second Messenger

Calcium Ion as a Second Messenger

Calcium ion (Ca²⁺) is involved in another ubiquitous second-messenger scheme. Much of the calcium-mediated response depends on release of Ca²⁺ from intracellular reservoirs, similar to the release of Ca²⁺ from the sarcoplasmic reticulum in the action of the neuromuscular junction. A component of the inner layer of the phospholipid bilayer, phosphatidylinositol 4,5-bisphosphate (PIP₂), is also required in this scheme (Figure 24.12).

When the external trigger binds to its receptor on the cell membrane, it activates phospholipase C, which hydrolyzes PIP₂ to inositol 1,4,5-triphosphate (IP₃) and a diacylglycerol (DAG), in a process mediated by a differentmember of the family of G proteins. The IP₃ is the actual second messenger. It diffuses through the cytosol to the endoplasmic reticulum (ER), where it stimulates the release of Ca²⁺. A complex is formed between the calcium-binding protein calmodulin and Ca²⁺. This calcium–calmodulin complex activates a cyto-solic protein kinase, which phosphorylates target enzymes in the same fashion as in the cAMP second-messenger scheme. DAG also plays a role in this scheme; it is nonpolar and diffuses through the plasma membrane. When DAG encoun-ters the membrane-bound protein kinase C, it too acts as a second messenger by activating this enzyme (actually a family of enzymes). 

Protein kinase C also phosphorylates target enzymes, including channel proteins that control the flow of Ca²⁺ into and out of the cell. By controlling the flow of Ca²⁺, this second-messenger system can produce sustained responses even when the supply of Ca²⁺ in the intracellular reservoirs becomes exhausted.