{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T22:16:14Z","timestamp":1758924974065},"reference-count":54,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,1,10]]},"abstract":"<jats:p>Antigen-evoked influx of extracellular Ca2+ into mast cells may occur via store-operated Ca2+ channels called calcium release\u2013activated calcium (CRAC) channels. In mast cells of the rat basophilic leukemia cell line (RBL-2H3), cholera toxin (CT) potentiates antigen-driven uptake of 45Ca2+ through cAMP-independent means. Here, we have used perforated patch clamp recording at physiological temperature to test whether cholera toxin or its substrate, Gs, directly modulates the activity of CRAC channels. Cholera toxin dramatically amplified (two- to fourfold) the Ca2+ release\u2013activated Ca2+ current (ICRAC) elicited by suboptimal concentrations of antigen, without itself inducing ICRAC, and this enhancement was not mimicked by cAMP elevation. In contrast, cholera toxin did not affect the induction of ICRAC by thapsigargin, an inhibitor of organelle Ca2+ pumps, or by intracellular dialysis with low Ca2+ pipette solutions. Thus, the activity of CRAC channels is not directly controlled by cholera toxin or Gs\u03b1. Nor was the potentiation of ICRAC due to enhancement of phosphoinositide hydrolysis or calcium release. Because Gs and the A subunit of cholera toxin bind to ADP ribosylation factor (ARF) and could modulate its activity, we tested the sensitivity of antigen-evoked ICRAC to brefeldin A, an inhibitor of ARF-dependent functions, including vesicle transport. Brefeldin A blocked the enhancement of antigen-evoked ICRAC without inhibiting ADP ribosylation of Gs\u03b1, but it did not affect ICRAC induced by suboptimal antigen or by thapsigargin. These data provide new evidence that CRAC channels are a major route for Fc\u03b5 receptor I\u2013triggered Ca2+ influx, and they suggest that ARF may modulate the induction of ICRAC by antigen.<\/jats:p>","DOI":"10.1083\/jcb.148.1.137","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:45:41Z","timestamp":1027701941000},"page":"137-146","update-policy":"http:\/\/dx.doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Potentiation of Fc\u03b5 Receptor I\u2013activated Ca2+ Current (I<i>CRAC<\/i>) by Cholera Toxin: Possible Mediation by ADP Ribosylation Factor"],"prefix":"10.1083","volume":"148","author":[{"given":"Michael A.","family":"McCloskey","sequence":"first","affiliation":[{"name":"Department of Zoology and Genetics, and Signal Transduction Training Group, Iowa State University, Ames, Iowa 50011-3223"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Zoology and Genetics, and Signal Transduction Training Group, Iowa State University, Ames, Iowa 50011-3223"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2000,1,10]]},"reference":[{"key":"2023072902064947600_b1-1480137","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1042\/bj3040431","article-title":"Antigen and thapsigargin promote influx of Ca2+ in rat basophilic RBL-2H3 cells by ostensibly similar mechanisms that allow filling of inositol 1,4,5-trisphosphate-sensitive and mitochondrial Ca2+ stores","volume":"304","author":"Ali","year":"1994","journal-title":"Biochem. 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