Mechanisms of capacitative calcium entry

Abstract

Capacitative Ca2+ entry involves the regulation of plasma membrane Ca2+ channels by the filling state of intracellular Ca2+ stores in the endoplasmic reticulum (ER). Several theories have been advanced regarding the mechanism by which the stores communicate with the plasma membrane. One such mechanism, supported by recent findings, is conformational coupling: inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) receptors in the ER may sense the fall in Ca2+ levels through Ca2+-binding sites on their lumenal domains, and convey this conformational information directly by physically interacting with Ca2+ channels in the plasma membrane. In support of this idea, in some cell types, store-operated channels in excised membrane patches appear to depend on the presence of both Ins(1,4,5)P3 and Ins(1,4,5)P3 receptors for activity; in addition, inhibitors of Ins(1,4,5)P3 production that either block phospholipase C or inhibit phosphatidylinositol 4-kinase can block capacitative Ca2+ entry. However, the electrophysiological current underlying capacitative Ca2+ entry is not blocked by an Ins(1,4,5)P3 receptor antagonist, and the blocking effects of a phospholipase C inhibitor are not reversed by the intracellular application of Ins(1,4,5)P3. Furthermore, cells whose Ins(1,4,5)P3 receptor genes have been disrupted can nevertheless maintain their capability to activate capacitative Ca2+ entry channels in response to store depletion. A tentative conclusion is that multiple mechanisms for signaling capacitative Ca2+ entry may exist, and involve conformational coupling in some cell types and perhaps a diffusible signal in others.

Ca 2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca 2+ uniporter gene MCU

“…Ca 2+ released by IP 3 Rs is rapidly cleared by plasma membrane (PM)-localized components and mitochondria, which decreases Ca 2+ available for SERCA pumps to refill stores (22,23,(51)(52)(53)(54)(55)(56). These combined effects lead to extensive ER store depletion and an activation of CRAC channels (57,58).…”

Effects of Azaspiracids 2 and 3 on Intracellular cAMP, [Ca2+], and pH

“…Ca 2+ entry can be signaled by a variety of processes, including direct activation by surface receptors and indirect activation by second messengers. The most commonly observed mechanism of calcium entry in nonexcitable cells is capacitative calcium influx or SOC entry (27). However, other noncapacitative calcium influx mechanisms have been described in lymphocytes: plasmatic membrane inositol trisphosphate receptor (40), nonvoltage-dependent channels (similar to L type channels), nicotinic acid adenine dinucleotide phosphate receptor, anexins, or CD20 have been described as calcium channels (28); up till now, their functional importance was not clear.…”

“…In Jurkat T cells, the SOC influx is brought about by opening of the Ca 2+ release-activated Ca 2+ () and Ca 2+ release-activated nonselective cation channels (); however, in human T cells, the mechanism by which SOC influx is brought about is still not well-understood. Indeed, the molecular identity of SOC channels and its precise activation mechanism remain undefined ( , ). They are typically activated by the depletion of calcium from internal stores, but the initiating stimulus can be from a different nature: surface receptor engagement, inositol 1,4,5-trisphophate production, SERCA inhibition, the presence of ionophores, or dialysis of the cytoplasm with Ca 2+ buffers (); hence, all of these possibilities are available to explain AZ-2 action.…”

Shear-Induced Nitric Oxide Production by Endothelial Cells

“…where k rel , k res , k out , k 1 , k 3 and k 5 are rate constants. Influx of calcium ions from the extracellular fluid into the cytosol occurs through both MSICs (12,59) and CCE (32). The corresponding calcium fluxes are related by…”

“…where q max is the maximal rate of influx, W (τ ) quantifies the extent to which the applied mechanical force is converted to gating energy for MSICs, and the constant χ = 28.6 dynes/cm 2 represents the membrane shear modulus. The flux due to CCE, q CCE , is caused by the depletion of internal calcium stores, which induces influx of calcium from the extracellular fluid (32). The magnitude of q CCE is affected by cGMP (40,60), such that (12,59,60)…”