The stretch-activated channel blocker Gd(3+) reduces palytoxin toxicity in primary cultures of skeletal muscle cells.
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 Ca(2+) response triggered by PLTX and the development of myotoxic insult. Ca(2+) imaging experiments revealed that PLTX causes a transitory intracellular Ca(2+) response (transient phase) followed by a slower and more sustained Ca(2+) increase (long-lasting phase). The transient phase is due to Ca(2+) release from intracellular stores and entry through voltage-dependent channels and the Na(+)/Ca(2+) exchanger (reverse mode). The long-lasting phase is due to a massive and prolonged Ca(2+) 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 Ca(2+) 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.
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
Giorgia
G
Del Favero
Chiara
C
Florio
Barbara
B
Codan
Silvio
S
Sosa
Mark
M
Poli
Orfeo
O
Sbaizero
Jordi
J
Molgó
Aurelia
A
Tubaro
Paola
P
Lorenzon
D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003064:Cnidarian Venoms; D005682:Gadolinium / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D000095702:Polyether Toxins
D000178:Acrylamides; D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003064:Cnidarian Venoms; D005682:Gadolinium; D019831:Sodium-Calcium Exchanger; C010272:palytoxin; D000095702:Polyether Toxins