title: Effects of palytoxin on cation occlusion and phosphorylation of the (Na+,K+)-ATPase.
abstract: Palytoxin (PTX) inhibits the (Na(+) + K+)-driven pump and simultaneously opens channels that are equally permeable to Na+ and K+ in red cells and other cell membranes. In an effort to understand the mechanism by which PTX induces these fluxes, we have studied the effects of PTX on: 1) K+ and Na+ occlusion by the pump protein; 2) phosphorylation and dephosphorylation of the enzyme when a phosphoenzyme is formed from ATP and from P(i); and 3) p-nitro phenyl phosphatase (p-NPPase) activity associated with the (Na+, K+)-ATPase. We have found that palytoxin 1) increases the rate of deocclusion of K+(Rb+) in a time- and concentration-dependent manner, whereas Na+ occluded in the presence of oligomycin is unaffected by the toxin; 2) makes phosphorylation from P(i) insensitive to K+, and 3) stimulates the p-NPPase activity. The results are consistent with the notion that PTX produces a conformation of the Na+, K(+)-pump that resembles the one observed when ATP is bound to its low-affinity binding site. Further, they suggest that the channels that are formed by PTX might arise as a consequence of a perturbation in the ATPase structure, leading to the loss of control of the outside "gate" of the enzyme and hence to an uncoupling of the ion transport from the catalytic function of the ATPase.
authors.affiliation: Laboratory for Membrane Transport, Department of Cell Biology, Harvard Medical School, One Kendall Square, Building 600 Third Floor, Cambridge, MA 02139, USA. mtosteson@hms.harvard.edu
authors.forename: M T
authors.initials: MT
authors.lastname: Tosteson
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Arnadottir
authors.forename: D C
authors.initials: DC
authors.lastname: Tosteson
mesh_terms: D009597:4-Nitrophenylphosphatase / Q000737:chemistry*; D000178:Acrylamides / Q000737:chemistry*; D002412:Cations / Q000737:chemistry; D003064:Cnidarian Venoms; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015640:Ion Channel Gating; D010758:Phosphorus / Q000737:chemistry; D010766:Phosphorylation; D011188:Potassium / Q000737:chemistry*; D012413:Rubidium / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry*; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry*; D000095702:Polyether Toxins
chemical_list: D009597:4-Nitrophenylphosphatase; D000178:Acrylamides; D002412:Cations; D003064:Cnidarian Venoms; D010758:Phosphorus; D011188:Potassium; D012413:Rubidium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; C010272:palytoxin; D000095702:Polyether Toxins