Depletion of Intracellular Calcium Stores Activates a Calcium Conducting Nonselective Cation Current in Mouse Pancreatic Acinar Cells

Krause, Elmar; Pfeiffer, Fatima; Schmid, Andreas; Schulz, Irene

doi:10.1074/jbc.271.51.32523

Cited by 102 publications

(70 citation statements)

References 40 publications

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“…When the cytosolic Ca 2ϩ concentration rises, the plasma membrane Ca 2ϩ -ATPase pump is invariably activated to extrude Ca 2ϩ , and in the absence of compensatory Ca 2ϩ entry from the extracellular space, cells would inevitably run out of stored Ca 2ϩ . The molecular structures of the channels responsible for Ca 2ϩ entry are not known, but Ca 2ϩ -selective and non-selective cation influx pathways have been described (42,43). It will be interesting to study the contribution of CaT-L to these pathways and its role in Ca 2ϩ secretion coupling in pancreatic acinar cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of CaT-like, a Novel Calcium-selective Channel, Correlates with the Malignancy of Prostate Cancer

Wissenbach¹,

Niemeyer²,

Fixemer

et al. 2001

Journal of Biological Chemistry

263

232

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The regulation of intracellular Ca 2؉ plays a key role in the development and growth of cells. Here we report the cloning and functional expression of a highly calciumselective channel localized on the human chromosome 7. The sequence of the new channel is structurally related to the gene product of the CaT1 protein cloned from rat duodenum and is therefore called CaT-like (CaT-L). CaT-L is expressed in locally advanced prostate cancer, metastatic and androgen-insensitive prostatic lesions but is undetectable in healthy prostate tissue and benign prostatic hyperplasia. Additionally, CaT-L is expressed in normal placenta, exocrine pancreas, and salivary glands. New markers with well defined biological function that correlate with aberrant cell growth are needed for the molecular staging of cancer and to predict the clinical outcome. The human CaT-L channel represents a marker for prostate cancer progression and may serve as a target for therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Expression of CaT-like, a Novel Calcium-selective Channel, Correlates with the Malignancy of Prostate Cancer

Wissenbach¹,

Niemeyer²,

Fixemer

et al. 2001

Journal of Biological Chemistry

263

232

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“…There are a number of examples of store-operated Ca 2+ entry that have properties distinct from I crac (e.g. Krause et al, 1996;Trepakova et al, 2000), others are reviewed in Parekh and Putney (Parekh and Putney, 2005), and perhaps TRPCs function as store-operated channels in such instances.…”

Section: The Trp Storymentioning

confidence: 99%

New molecular players in capacitative Ca2+ entry

Putney

2007

Journal of Cell Science

144

112

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Capacitative Ca2+ entry links the emptying of intracellular Ca2+ stores to the activation of store-operated Ca2+ channels in the plasma membrane. In the twenty years since the inception of the concept of capacitative Ca2+ entry, a number of activation mechanisms have been proposed, and there has been considerable interest in the possibility that TRP channels function as store-operated channels. However, in the past two years, two major players in both the signaling and permeation mechanisms for store-operated channels have been discovered: Stim1 and the Orai proteins. Stim1 is an endoplasmic reticulum Ca2+ sensor. It appears to act by redistributing within a small component of the endoplasmic reticulum, approaching the plasma membrane, but does not seem to translocate into the plasma membrane. Stim1 signals to plasma membrane Orai proteins, which constitute pore-forming subunits of store-operated channels.

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“…This mechanism also operates in the pancreatic acinar cells, because stimulant-elicited release of Ca 2+ from the ER results in translocation of STIM1 to puncta close to the basolateral plasma membrane, specifically at locations where the ER is devoid of ribosomes and where interaction between STIM1 and Orai1 therefore occurs (19). Despite this, electrophysiological investigations of the currents evoked by Ca 2+ store depletion have so far failed to provide evidence for the existence in pancreatic acinar cells of Ca 2+ -selective currents of the CRAC type (20)(21)(22) originally discovered in mast cells (23), although activation of nonselective currents were shown (21,22). Therefore, although the linkage between agonist-evoked Ca 2+ release from the ER and store-operated Ca 2+ entry, through STIM1 and Orai1, is established for the pancreatic acinar cells (19), there is uncertainty about the biophysical nature of the principal Ca 2+ entry channels.…”

mentioning

confidence: 99%

Ca ²⁺ release-activated Ca ²⁺ channel blockade as a potential tool in antipancreatitis therapy

Gerasimenko

Gryshchenko

Ferdek

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

171

225

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Alcohol-related acute pancreatitis can be mediated by a combination of alcohol and fatty acids (fatty acid ethyl esters) and is initiated by a sustained elevation of the Ca 2+ concentration inside pancreatic acinar cells ([Ca 2+ ] i ), due to excessive release of Ca 2+ stored inside the cells followed by Ca 2+ entry from the interstitial fluid. The sustained [Ca 2+ ] i elevation activates intracellular digestive proenzymes resulting in necrosis and inflammation. We tested the hypothesis that pharmacological blockade of store-operated or Ca 2+ release-activated Ca 2+ channels (CRAC) would prevent sustained elevation of [Ca 2+ ] i and therefore protease activation and necrosis. In isolated mouse pancreatic acinar cells, CRAC channels were activated by blocking Ca 2+ ATPase pumps in the endoplasmic reticulum with thapsigargin in the absence of external Ca 2+ . Ca 2+ entry then occurred upon admission of Ca 2+ to the extracellular solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A, inhibited store-operated Ca 2+ entry in a concentrationdependent manner within the range of 1 to 50 μM (IC 50 = 3.4 μM), but had little or no effect on the physiological Ca 2+ spiking evoked by acetylcholine or cholecystokinin. Palmitoleic acid ethyl ester (100 μM), an important mediator of alcohol-related pancreatitis, evoked a sustained elevation of [Ca 2+ ] i , which was markedly reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced trypsin and protease activity as well as necrosis were almost abolished by blocking CRAC channels. There is currently no specific treatment of pancreatitis, but our data show that pharmacological CRAC blockade is highly effective against toxic [Ca 2+ ] i elevation, necrosis, and trypsin/protease activity and therefore has potential to effectively treat pancreatitis.capacitative Ca 2+ entry | alcohol metabolite | pancreas | hepatocyte Ca 2+ entry | AR42JA cute pancreatitis is a human disease mostly caused by alcohol abuse or complications from biliary disease. In this disease, against which there is currently no effective therapy, digestive proenzymes are prematurely activated inside the acinar cells leading to autodigestion and necrosis (1-3). Intracellular Ca 2+ plays a critical role in the initiation of this disease process (2-4), but intracellular Ca 2+ also plays a critical role in the physiological regulation of the normal exocytotic secretion of the digestive proenzymes (5).The pancreatic acinar cells are capable of generating multiple patterns of cytosolic Ca 2+ signals depending on the type and concentration of the stimulating agent (5). The physiological Ca 2+ signals regulating secretion-evoked by the neurotransmitter acetylcholine (ACh) or the hormone cholecystokinin (CCK)-consist of repetitive short-lasting rises in the cytosolic Ca 2+ concentration ([Ca 2+ ] i ). These are mostly confined to the apical area, in which the secretory (zymogen) granules (ZGs) are concentrated, by a belt of perigranular mitochondria operating as a firewall against...

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Depletion of Intracellular Calcium Stores Activates a Calcium Conducting Nonselective Cation Current in Mouse Pancreatic Acinar Cells

Cited by 102 publications

References 40 publications

Expression of CaT-like, a Novel Calcium-selective Channel, Correlates with the Malignancy of Prostate Cancer

Expression of CaT-like, a Novel Calcium-selective Channel, Correlates with the Malignancy of Prostate Cancer

New molecular players in capacitative Ca2+ entry

Ca ²⁺ release-activated Ca ²⁺ channel blockade as a potential tool in antipancreatitis therapy

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Depletion of Intracellular Calcium Stores Activates a Calcium Conducting Nonselective Cation Current in Mouse Pancreatic Acinar Cells

Cited by 102 publications

References 40 publications

Expression of CaT-like, a Novel Calcium-selective Channel, Correlates with the Malignancy of Prostate Cancer

Expression of CaT-like, a Novel Calcium-selective Channel, Correlates with the Malignancy of Prostate Cancer

New molecular players in capacitative Ca2+ entry

Ca 2+ release-activated Ca 2+ channel blockade as a potential tool in antipancreatitis therapy

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Product

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Ca ²⁺ release-activated Ca ²⁺ channel blockade as a potential tool in antipancreatitis therapy