Another dimension to calcium signaling: a look at extracellular calcium

Abstract

Cell biologists know the calcium ion best as a vital intracellular second messenger that governs countless cellular functions. However, the recent identification of cell-surface detectors for extracellular Ca2+ has prompted consideration of whether Ca2+ also functions as a signaling molecule in the extracellular milieu. The cast of Ca2+ sensors includes the well-characterized extracellular-Ca2+-sensing receptor, a G-protein-coupled receptor originally isolated from the parathyroid gland. In addition, other receptors, channels and membrane proteins, such as gap junction hemichannels, metabotropic glutamate receptors, HERG K+ channels and the receptor Notch, are all sensitive to external [Ca2+] fluctuations. A recently cloned Ca2+ sensor (CAS) in Arabidopsis extends this concept to the plant kingdom. Emerging evidence indicates that [Ca2+] in the local microenvironment outside the cell undergoes alterations potentially sufficient to exert biological actions through these sensor proteins. The extracellular space might therefore constitute a much more dynamic Ca2+ signaling compartment than previously appreciated.

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

“…Similarly, the expressions of orthologs of G o ligands, (egl-8, egl-30, goa-1, and dgk-1) that are essential for chemotaxis apart from regulation of healthspan of the nematode (Hofer 2005) also substantiate our findings. An ortholog of the heterotrimeric G protein alpha subunit Gq, egl-30, (Wang and Wadsworth 2002) and its downstream player, egl-8, (Ziegler et al 2009) in C. elegans plays a pivotal role in regulating pharyngeal pumping, egg laying and locomotion (Govorunova et al 2010).…”

A Novel Calcium Binding Site in the Slow Vacuolar Cation Channel TPC1 Senses Luminal Calcium Levels

“…Potassium, as well as sodium content (under salt stress), can reach levels greater than 100 mM (Beyhl et al, 2009;Rienmü ller et al, 2010), whereas luminal free calcium concentrations can get to 1 mM (Pottosin and Schö nknecht, 2007). While the vacuolar Ca 2+ concentration is more than 1000-fold higher compared with the cytosol, fluctuations of the extracytosolic Ca 2+ concentration may exert biological actions, as has been demonstrated for extracellular calcium fluctuations (Han et al, 2003;Hofer, 2005).…”

“…Comparable to TPC1, in HERG channels, small changes in external calcium concentration shift the voltage dependence of channel activation to more positive membrane potentials without affecting gating charge. Using site-directed mutagenesis, two adjacent negatively charged amino acids in the S3-S4 linker, near the S4 voltage sensor of the HERG channel, were identified as participating in low-affinity binding sites that regulate voltage and Ca 2+ dependence of the channel (Johnson et al, 2001;Hofer, 2005). To refine our model, future mutagenesis studies will have to explore whether TPC1 sites related to those that govern HERG gating are addressed via Glu-456 and Glu-457.…”

Emergence of a spermine-sensitive, non-inactivating conductance in mature hippocampal CA1 pyramidal neurons upon reduction of extracellular Ca2+: Dependence on intracellular Mg2+ and ATP

“…At this juncture, it is not known how the other Ca 2+ sensing mechanisms that are found in the hippocampus, such as voltage-dependent Ca 2+ channels, mGluRs or hemi-gap channels (Hofer 2005) may contribute to the observations recorded here. One interesting possibility is that the sustained conductance that we record on the pyramidal neurons is due to one or more members of the transient receptor potential (TRP) family .…”

“…Fluctuations in [Ca 2+ ] e are sensed by a range of plasma membrane Ca 2+ -sensing receptors and ion channels (Hofer 2005). Furthermore, the voltage dependence of many types of monovalent ion channels is shifted in the absence of divalent cations.…”