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

Abstract

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. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 146–157, 1998

Cell Types, Network Homeostasis, and Pathological Compensation from a Biologically Plausible Ion Channel Expression Model

“…An important readout signal appears to be intracellular [Ca 2+ ], which correlates with electrical activity due to voltage-dependent Ca 2+ channels and buffering mechanisms that average out fluctuations in time and space (Berridge 1998; Wheeler et al, 2012). Moreover, long-term changes in [Ca 2+ ] are found to regulate many ion channel types (Barish 1998; Mermelstein et al, 2000; O’Leary et al, 2010; Turrigiano et al, 1994; Wheeler et al, 2012). …”

Energy-efficient network activity from disparate circuit parameters

“…While our study characterizes which parameter configurations are energy efficient, we did not study the mechanisms of how biological circuits would modulate their conductances in order to arrive at these configurations. Long-term changes in intracellular calcium have been found to regulate many ion channels ( 53 – 55 ); thus, it is possible that intracellular calcium is used to tune conductances for energy efficiency. In our study, we found that intracellular calcium level is linearly related to energy consumption across circuit configurations that match experimental data ( SI Appendix , Fig.…”

Altered Calcium Signaling Following Traumatic Brain Injury

“…These homeostatic mechanisms maintain [Ca 2+ ] i at low levels, usually about 100 nM in neurons compared to an extracellular concentration of approximately 1 mM. Maintaining [Ca 2+ ] i at such low levels in the cell allows relatively small or localized increases in [Ca 2+ ] i to be used as a trigger to activate signal transduction pathways which lead to physiological processes such as activation of specific enzymes or modulation of ion channels (Racay and Lehotsky, 1996; Tymianski and Tator, 1996; Barish, 1998; Weber, 2004). …”

“…An individual neuron may have several different types of VGCCs and ROCs, and Ca 2+ influx through specific channels is quite important. For example, certain classes of VGCCs trigger neurotransmitter release at synaptic terminals (Robitaille et al, 1990; Augustine et al, 1991; Robitaille et al, 1993; Wu et al, 1998), and specific ionotropic glutamate receptors can lead to Ca 2+ -dependent gene induction (Bading et al, 1993; Lerea and McNamara, 1993; Barish, 1998). …”