Pre-translational regulation of the (Na+ + K+)-ATPase in response to demand for ion transport in cultured chicken skeletal muscle. 1990

J P Taormino, and D M Fambrough
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218.

The expression of the (Na+ + K+)-ATPase in cultured chicken skeletal muscle can be altered by varying the demand for ion transport. Veratridine, an activator of voltage-sensitive Na+ channels, causes a specific transient increase in biosynthesis of the sodium pump that accounts for the doubling of the number of (Na+ + K+)-ATPase molecules in the sarcolemma (Wolitzky, B.A., and Fambrough, D.M. (1986) J. Biol. Chem. 261, 9990-9999). Here we report a study of veratridine-induced up-regulation, focusing upon alpha- and beta-mRNA levels and transcription rates. Myotubes normally express the alpha 1-isoform mRNA and the beta-mRNA at a molar ratio of 0.6 +/- 0.1 (S.D.). In the presence of veratridine, the beta-mRNA is transiently up-regulated approximately 3-fold. The kinetics of this increase parallel the rate of beta-subunit protein synthesis. The increase in beta-mRNA during up-regulation is accomplished by an increase in the transcription rate of the beta gene. The veratridine-induced increase in beta-mRNA is not blocked by cycloheximide. The alpha-mRNA also increases during exposure to veratridine, but this increase is very modest and occurs very late in the up-regulation process. The increased beta-mRNA results in over-production of beta-subunits, which we postulate drives more efficient assembly of alpha beta complexes, i.e. sodium pump molecules. As the up-regulated state is achieved the level of beta-mRNA falls abruptly, reflecting a marked decrease in beta-mRNA stability. Treatment of up-regulated myotubes with tetrodotoxin, a veratridine antagonist, results in rapid down-regulation of the sodium pump, while having little or no effect on the levels of alpha 1- and beta-mRNAs.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick
D000254 Sodium-Potassium-Exchanging ATPase An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients. ATPase, Sodium, Potassium,Adenosinetriphosphatase, Sodium, Potassium,Na(+)-K(+)-Exchanging ATPase,Na(+)-K(+)-Transporting ATPase,Potassium Pump,Sodium Pump,Sodium, Potassium ATPase,Sodium, Potassium Adenosinetriphosphatase,Sodium-Potassium Pump,Adenosine Triphosphatase, Sodium, Potassium,Na(+) K(+)-Transporting ATPase,Sodium, Potassium Adenosine Triphosphatase,ATPase Sodium, Potassium,ATPase, Sodium-Potassium-Exchanging,Adenosinetriphosphatase Sodium, Potassium,Pump, Potassium,Pump, Sodium,Pump, Sodium-Potassium,Sodium Potassium Exchanging ATPase,Sodium Potassium Pump
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated

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