Calcium as Second Messengers - Essay Example

Calcium ions are also important intracellular messengers. In fact, calcium ions are probably the most widely used intracellular messengers (Kimball, 2006). Calcium plays a fundamental role in a variety of cellular functions. It is involved in contraction, secretion, endocytosis, transport across membranes and in more general processes such as cell motility, cell growth and cell division (De Robertis & De Robertis, 1987). Calcium is one of the most important second messenger molecules, with a diverse array of effectors.

The intracellular Ca2+ plays a role as the second messenger in the hypotonic stress-induced Na+ transport by stimulating the transcription of SGK1 and ENaC subunits (Taruno, Niisato, Marunaka, 2007). Calcium directly moderates electrical activity, on a relatively fast time scale, through its control of calcium-dependent potassium channels. Long term effects are mediated by various kinases and phosphatases. Calcium is one of the activators of protein kinase C, which plays a role in synaptic plasticity.

In a complex with calmodulin56, calcium is an activator or regulator of several enzymes, including calcium-calmodulin dependent protein kinase, which plays a role in synaptic plasticity, and adenylate cyclase, which produces cAMP, another important second messenger. . Once Ca2+ was recognized as a carrier of signals, it became important to understand how its concentration within cells was regulated. Reversible complexation to specific ligands soon emerged as the only reasonable means to perform the task.

A number of small cell ligands bind Ca2+ with low affinity, but the process needed complex ligands able to complex Ca2+ with the specificity and affinity demanded by the intracellular ambient. A breakthrough in this direction was the solution of the crystal structure of parvalbumin by Kretsinger in 1972. This still functionally mysterious Ca2+ binding protein was to become the progenitor of a family of proteins known as EF hand proteins, which has now grown to nearly 600 members. EF hand proteins do buffer Ca2+ but also play another important role: They decode the information carried by Ca2+ and pass it on to targets.

They do so by changing conformation after binding Ca2+ and after interacting with targets. Essentially, EF hand proteins become more hydrophobic on the surface after complexing Ca2+, approach the target, and collapse around its binding domain. Thus, these proteins are better defined as Ca2+ modulated proteins, or Ca2+ sensors (Carafoli, 2002). Second messenger pathways, and some mechanisms controlling calcium concentration, are modeled as a series of bimolecular reactions, enzymatic reactions, and diffusion.

These processes occur both in compartments where the number of molecules are large enough to describe reactions deterministically (e.g. cell body), and in compartments where the number of molecules is small enough that reactions occur stochastically (e.g. spines). Thus, to model and simulate second messenger pathways in neurons requires algorithms for both diffusion and reactions, both