Functional role of the N-terminus of Na(+),K(+)-ATPase alpha-subunit as an inactivation gate of palytoxin-induced pump channel.
The N-terminus of the Na(+),K(+)-ATPase alpha-subunit shows some homology to that of Shaker-B K(+) channels; the latter has been shown to mediate the N-type channel inactivation in a ball-and-chain mechanism. When the Torpedo Na(+),K(+)-ATPase is expressed in Xenopus oocytes and the pump is transformed into an ion channel with palytoxin (PTX), the channel exhibits a time-dependent inactivation gating at positive potentials. The inactivation gating is eliminated when the N-terminus is truncated by deleting the first 35 amino acids after the initial methionine. The inactivation gating is restored when a synthetic N-terminal peptide is applied to the truncated pumps at the intracellular surface. Truncated pumps generate no electrogenic current and exhibit an altered stoichiometry for active transport. Thus, the N-terminus of the alpha-subunit appears to act like an inactivation gate and performs a critical step in the Na(+),K(+)-ATPase pumping function.
Wu
Chau H
CH
Department of Molecular Pharmacology and Biological Chemistry (S-215), The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611-3008, USA. c-wu@northwestern.edu
Vasilets
Larisa A
LA
Takeda
Kazuo
K
Kawamura
Masaru
M
Schwarz
Wolfgang
W
D000178:Acrylamides / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D003064:Cnidarian Venoms; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects*; D017386:Sequence Homology, Amino Acid; D051637:Shaker Superfamily of Potassium Channels; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*; D014101:Torpedo; D014981:Xenopus; D000095702:Polyether Toxins
D000178:Acrylamides; D003064:Cnidarian Venoms; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D000254:Sodium-Potassium-Exchanging ATPase; C010272:palytoxin; D000095702:Polyether Toxins