Actions of palytoxin on Na+ and Ca2+ homeostasis in human osteoblast-like Saos-2 cells.
Palytoxin (PTx) is a potent membrane-active agent produced by marine coelenterates that acts to stimulate bone resorption in organ culture at nanomolar concentrations. We report here the actions of PTx on Na+ and Ca2+ homeostasis in human osteoblast-like Saos-2 cells. PTx induced a rise in the cytosolic free Na+ concentration ([Na]i) by causing entry of extracellular Na+ (Na(e)+). PTx also caused a concentration-dependent biphasic rise in the cytosolic free Ca2+ concentration ([Ca2+]i) by enhancing entry of extracellular Ca2+ (Ca(e)2+). Entry of Na+ was dependent on the presence of Ca(e)2+ and was prevented by the Na+/Ca2+ exchange antagonist 3,4-dichlorobenzamil (DCB). Entry of Ca2+ was dependent on the presence of Na(e)+ but was not prevented by DCB. The actions of PTx on [Na+]i and [Ca2+]i were completely inhibited by pretreatment of the cells with ouabain. Ouabain alone had no acute effect on [Na+]i or [Ca2+]i in Saos-2 cells. We propose that interaction of PTx with the Na+ pump created a channel that allowed influx of Na(e)+ and Ca(e)2+. The rise in [Ca2+]i then stimulated the activity of the plasma membrane Na+/Ca2+ exchanger, which further enhanced Na(e)+ entry.
Monroe
J J
JJ
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts, USA.
Tashjian
A H
AH
D000178:Acrylamides / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003064:Cnidarian Venoms / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D010006:Osteoblasts / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D000095702:Polyether Toxins
D000178:Acrylamides; D002118:Calcium; D003064:Cnidarian Venoms; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; C010272:palytoxin; D000095702:Polyether Toxins