Receptor-activated Ca2+ inflow in animal cells: a variety of pathways tailored to meet different intracellular Ca2+ signalling requirements

Abstract

Receptor-activated Ca2+ channels (RACCs) play a central role in regulation of the functions of animal cells. Together with voltage-operated Ca2+ channels (VOCCs) and ligand-gated non-selective cation channels, RACCs provide a variety of pathways by which Ca2+ can be delivered to the cytoplasmic space and the endoplasmic reticulum (ER) in order to initiate or maintain specific types of intracellular Ca2+ signal. Store-operated Ca2+ channels (SOCs), which are activated by a decrease in Ca2+ in the ER, are a major subfamily of RACCs. A careful analysis of the available data is required in order to discern the different types of RACCs (differentiated chiefly on the basis of ion selectivity and mechanism of activation) and to properly develop hypotheses for structures and mechanisms of activation. Despite much intensive research, the structures and mechanisms of activation of RACCs are only now beginning to be understood. In considering the physiological functions of the different RACCs, it is useful to consider the specificity for Ca2+ of each type of cation channel and the rate at which Ca2+ flows through a single open channel; the locations of the channels on the plasma membrane (in relation to the ER, cytoskeleton and other intracellular units of structure and function); the Ca2+-responsive enzymes and proteins; and the intracellular buffers and proteins that control the distribution of Ca2+ in the cytoplasmic space. RACCs which are non-selective cation channels can deliver Ca2+ directly to specific regions of the cytoplasmic space, and can also admit Na+, which induces depolarization of the plasma membrane, the opening of VOCCs and the subsequent inflow of Ca2+. SOCs appear to deliver Ca2+ specifically to the ER, thereby maintaining oscillating Ca2+ signals.

Chronic Lithium Treatment Attenuates Intracellular Calcium Mobilization

“…As TG induces store depletion through an IP 3 receptor (IP 3 R)-independent mechanism, the effect of lithium on this SOCE component is likely to be related to actions distinct from its well-established modulatory effect on PI signaling (Hallcher and Sherman, 1980;Berridge et al, 1982). The SOCE apparatus is complex, involving the orchestrated action of SOCC, IP 3 Rs, and SERCAs (Barritt, 1999;Putney et al, 2001). Functional interactions between mitochondria and ER can also influence Ca 2 þ mobilization through SOCE (Fall and Keizer, 2001).…”

“…Intracellular Ca 2 þ signaling and homeostasis are maintained by an intricate array of processes acting in concert (Berridge et al, 2000;Putney et al, 2001) including, for example, inositol trisphosphate (IP 3 )-and ryanodinestimulated release of Ca 2 þ from endoplasmic reticulum (ER) storage pools (Berridge, 1995;Barritt, 1999;Putney and Ribeiro, 2000), voltage-and ligand-gated ion channel mediated Ca 2 þ influx (Ghosh and Greenberg, 1995), storeoperated Ca 2 þ entry (SOCE) (Putney et al, 2001), plasma membrane and sarcoplasmic/ER Ca 2 þ -ATPase pumps (PMCAs and SERCAs) (Brini and Carafoli, 2000), and mitochondrial Ca 2 þ uptake, storage, and release (Brini and Carafoli, 2000;Fall and Keizer, 2001). Disturbances of intracellular Ca 2 þ signaling can critically affect cellular function due to calcium's essential role in vital cellular processes including gene expression (Ghosh and Greenberg, 1995), neurogenesis and plasticity (Mattson, 2000), and cell death (Szalai et al, 1999).…”

TRPC3 Mediates T-cell Receptor-dependent Calcium Entry in Human T-lymphocytes

“…Different PLC-dependent Ca 2ϩ entry pathways, including activation by second messengers like InsP 3 or arachidonic acid (reviewed in Ref. 11) coexist in one cell and might influence each other (12,13). In DT40 B lymphocytes, it was shown that cation entry involves not only store-operated channels but also a population of Ca 2ϩ channels requiring functional InsP 3 Rs (14).…”

Cch1 and Mid1 Are Functionally Required for Vegetative Growth under Low-Calcium Conditions in the Phytopathogenic Ascomycete Botrytis cinerea

“…Efflux of Ca 2ϩ from the cell can occur via ATPase-dependent Ca 2ϩ pumps and antiporters (countertransporters), while Ca 2ϩ entry occurs through transporters or channels (9)(10)(11). Ca 2ϩ -permeable channels are responsible for the passive flow of Ca 2ϩ across cell membranes into the cytosol.…”