Intracellular calcium regulation of channel and receptor expression in the plasmalemma: potential sites of sensitivity along the pathways linking transcription, translation, and insertion.

Nervous system development is "activity dependent"--activation of neurons controls their development, which controls their activation patterns, which will then influence their further development, and so on. A critical issue is thus the regulation of channel and receptor expression. For nerve cells, the presence of specialized Ca2+-permeable channels in the surface membrane provides a direct link between electrical activity and the intracellular Ca2+ ion concentration ([Ca2+]i), and in many instances [Ca2+]i is thought to link membrane activation and internal biosynthesis. In this context, Ca2+-permeable channels function as "activity sensors," transducing membrane activation by admitting Ca2+ rapidly, locally, and proportionately. In this review, I consider the potential of [Ca2+]i to regulate channel and receptor expression. I emphasize mechanisms by which the Ca2+ concentration of the cytosol and/or the Ca2+ concentrations of membrane-delimited Ca2+ sequestering organelles may influence biosynthetic processes. Here, I use "expression" in the most general sense of referring to the number and location of functional channels and receptors in the plasmalemma; regulation of expression is not limited to transcriptional regulation, but further encompasses translational and posttranslational processes. At the core is the notion of regulation by patterned oscillations in cytosolic [Ca2+], and, in a synchronous or contrapuntal manner, filling and depletion of a series of Ca2+-sequestering organelles--nuclear envelope, endoplasmic reticulum, Golgi, trans-Golgi network, and secretory vesicles--that all also have critical roles in biosynthesis of membrane proteins. These structures provide both an internal Ca2+ regulation and distribution system, and a scaffold for synthesis, targeting, and insertion of channels and receptors.