Calcium as intracellular messenger: sensitivity modulation, C-kinase pathway, and sustained cellular response.

A model of information flow in the calcium messenger system is presented. When Ca2+ serves as an intracellular messenger in cells exhibiting a sustained response to an extracellular messenger, there are two branches by which information flows from cell surface to cell interior: One operates via amplitude modulation of calmodulin-regulated reactions and the other via sensitivity modulation of the calcium-sensitive, phospholipid-dependent protein kinase, C-kinase. It is postulated that the calmodulin branch is largely responsible for initiating, and the C-kinase branch for sustaining, cellular response in cells displaying sustained responses. The role of the C-kinase branch in the calcium messenger system provides a type of gain control in the process of cell activation. It is but one element of several which provides a considerable degree of plasticity in the operation of this cellular control system. Both cAMP and the biologically active intermediates of arachidonic acid metabolism--prostaglandins, thromboxanes, prostacyclin, and leukotrienes--provide additional inputs into this messenger system and a means of extending its adaptability to specific control needs. In particular, in some cell types it is possible that the cAMP messenger system provides the means of achieving gain control in the calcium messenger system either as an alternative to the C-kinase branch of the calcium messenger system or as a supplemental pathway to it.