{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:43:48Z","timestamp":1790700228718,"version":"4.1.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p> The contractile force generated by hepatic stellate cells in response to endothelin-1 contributes to sinusoidal blood flow regulation and hepatic fibrosis. This study's aim was to directly test the widely held view that changes in cytosolic Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) mediate stellate cell force generation. Contractile force generation by primary cultures of rat hepatic stellate cells grown in three-dimensional collagen gels was directly and quantitatively measured using a force transducer. Stellate cell [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, myosin activation, and migration were quantified using standard techniques. [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> was modulated using ionomycin, BAPTA, KCl, and removal of extracellular Ca<jats:sup>2+<\/jats:sup>. Removal of extracellular Ca<jats:sup>2+<\/jats:sup> did not alter endothelin-1-stimulated force development or [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Ionomycin, a Ca<jats:sup>2+<\/jats:sup> ionophore, triggered an increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> that was three times greater than that stimulated by endothelin-1, but only induced 16% of the force and 38% of the myosin regulatory light chain (MLC) phosphorylation induced by endothelin-1. Physiological increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> induced by hyperkalemia had no effect on contractile force. Loading BAPTA, a Ca<jats:sup>2+<\/jats:sup> chelator, in stellate cells completely blocked endothelin-1-induced increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> but had no effect on endothelin-1-stimulated force generation or MLC phosphorylation. In contrast, Y-27632, a selective rho-associated kinase inhibitor, inhibited endothelin-1-stimulated force generation by at least 70% and MLC phosphorylation by at least 80%. Taken together, these observations indicate that changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> are neither necessary nor sufficient for contractile force generation by rat stellate cells. Our results challenge the current model of contractile regulation in hepatic stellate cells and have important implications for our understanding of hepatic pathophysiology. <\/jats:p>","DOI":"10.1152\/ajpgi.00337.2005","type":"journal-article","created":{"date-parts":[[2005,8,26]],"date-time":"2005-08-26T00:33:45Z","timestamp":1125016425000},"page":"G7-G13","source":"Crossref","is-referenced-by-count":37,"title":["[Ca<sup>2+<\/sup>]<sub>i<\/sub>-independent contractile force generation by rat hepatic stellate cells in response to endothelin-1"],"prefix":"10.1152","volume":"290","author":[{"given":"Andrew C.","family":"Melton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Hal F.","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.23500"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70368-4"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.279.5.L849"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510095"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Friedman SL. 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