Palytoxin modulates cytosolic ph in human osteoblast-like saos-2
cells via an interaction with the na+, k+-atpase.
Monroe, James J., and Armen H. Tashjian, Jr.
Department of Molecular and Cellular Toxicology, Harvard School of
Public Health, and Department of Biological Chemistry and Molecular
Pharmacology, Harvard Medical School, Boston MA 02115
APStracts 2:0386C, 1995.
Palytoxin at nM concentrations, enhances the permeability of mamalian
cell membranes to both Na+ and Ca2+. In basal human osteoblast-like
SaOS-2 cells, palytoxin (8 nM) caused a persistent decrease in
cytosolic pH (pHi) of about 0.2 units which required the presence of
extracellular Ca2+ (Ca2+e) and Na+ (Na+e). We acidified SaOS-2, cells
by incubation with nigericin, to examine the action of palytoxin in
cells with an activated Na+-H+ antiporter. Under these conditions,
palytoxin increased the pHi without requiring Ca2+e or Na+e, and the
alkalinization was unaffected by hexamethylene amiloride. We conclude
that the palytoxin-induced rise in pHi did not involve the Na+-H+
antiporter. Palytoxin increased the rate of 86Rb+ efflux. We propose
that palytoxin induced alkalinization in nigericin-acidified cells by
collapsing the K+ gradient. Exposure to ouabain had no effect on pHi
but it prevented the actions of palytoxin on pHi in both basal and
nigericin-acidified cells. Ouabain-resistant mutant cells were less
sensitive to palytoxin in extruding 86Rb+ than their ouabain
-sensitive parents. We conclude that palytoxin interacts with the Na+,
K+-ATPase to regulate pHi in both basal and nigericin-acidified SaOS
-2 cells.
Received 21 July 1995; accepted in final form 17 October 1995.
APS Manuscript Number C446-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95