Palytoxin modulates cytosolic pH in human osteoblast-like Saos-2 cells via an interaction with Na (+) -K (+) -ATPase
Monroe, J.J.; Tashjian, A.H.
American Journal of Physiology 270(5 Pt 1): C1277-C1283
1996
ISSN/ISBN: 0002-9513 PMID: 8967426 Document Number: 463013
Palytoxin (PTx) at nanomolar concentrations enhances the permeability of mammalian cell membranes to both Na+ and Ca-2+. In basal human osteoblast-like Saos-2 cells, PTx (8 nM) caused a persistent decrease in cytosolic pH (pH-i) of about 0.2 units, which required the presence of extracellular Ca-2+ (Ca-e-2+) and Na+ (Na-e+). We acidified Saos-2 cells by incubation with nigericin to examine the action of PTx in cells with an activated Na+/H+ antiporter. Under these conditions, PTx increased the pH-i without requiring Ca-2+ or Na-e+ and the alkalinization was unaffected by hexamethylene amiloride. We conclude that the PTx-induced rise in pH-i did not involve the Na+/H+ antiporter. PTx increased the rate of 86Rb+ efflux. We propose that PTx induced alkalinization in nigericin-acidified cells by collapsing the K+ gradient. Exposure to ouabain had no effect on pH-i, but it prevented the actions of PTx on pH-i in both basal and nigericin-acidified cells. Ouabain-resistant mutant cells were less sensitive to PTx in extruding 86Rb+ than their ouabain-sensitive parents. We conclude that PTx interacts with the Na+-K+-adenosine-triphosphatase to regulate pH-i in both basal and nigericin-acidified Saos-2 cells.