The Stretch-Activated Channel Blocker Gd3+ Reduces Palytoxin Toxicity in Primary Cultures of Skeletal Muscle Cells

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• 作者：Giorgia Del Favero ; Chiara Florio ; Barbara Codan ; Silvio Sosa ; Mark Poli ; Orfeo Sbaizero ; Jordi Molg贸 ; Aurelia Tubaro ; Paola Lorenzon
• 刊名：Chemical Research in Toxicology
• 出版年：2012
• 出版时间：September 17, 2012
• 年：2012
• 卷：25
• 期：9
• 页码：1912-1920
• 全文大小：434K
• 年卷期：v.25,no.9(September 17, 2012)
• ISSN：1520-5010

文摘

Palytoxin (PLTX) is one of the most toxic seafood contaminants ever isolated. Reports of human food-borne poisoning ascribed to PLTX suggest skeletal muscle as a primary target site. Primary cultures of mouse skeletal muscle cells were used to study the relationship between Ca²⁺ response triggered by PLTX and the development of myotoxic insult. Ca²⁺ imaging experiments revealed that PLTX causes a transitory intracellular Ca²⁺ response (transient phase) followed by a slower and more sustained Ca²⁺ increase (long-lasting phase). The transient phase is due to Ca²⁺ release from intracellular stores and entry through voltage-dependent channels and the Na⁺/Ca²⁺ exchanger (reverse mode). The long-lasting phase is due to a massive and prolonged Ca²⁺ influx from the extracellular compartment. Sulforhodamine B assay revealed that the long-lasting phase is the one responsible for the toxicity in skeletal muscle cells. Our data analyzed, for the first time, pathways of PLTX-induced Ca²⁺ entry and their correlation with PLTX-induced toxicity in skeletal muscle cells. The cellular morphology changes induced by PLTX and the sensitivity to gadolinium suggest a role for stretch-activated channels.