Coupling of the Na+/Ca2+ exchanger, Na+/K+ pump and sarcoplasmic reticulum in smooth muscle. 1993

E D Moore, and E F Etter, and K D Philipson, and W A Carrington, and K E Fogarty, and L M Lifshitz, and F S Fay
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605.

The Na+/Ca2+ exchanger, driven by a transmembrane Na+ gradient, plays a key role in regulating Ca2+ concentration in many cells. Although the exchanger influences Ca2+ concentration, its activity in smooth muscle appears to be closely coupled to Ca2+ availability from intracellular stores. This linkage might result if the exchanger were positioned close to Ca2+ storage sites within the sarcoplasmic reticulum. To test this hypothesis we have developed methods to assess the relative three-dimensional distribution of proteins involved in Na+/K+ pumping, Na+/Ca2+ exchange, Ca2+ storage within the sarcoplasmic reticulum, and attachment of contractile filaments to the membrane in smooth muscle. Here we report that the Na+/Ca2+ exchanger is largely co-distributed with the Na+/K+ pump on unique regions of the plasma membrane in register with, and close to, calsequestrin-containing regions of the sarcoplasmic reticulum in sites distinct from the sites where contractile filaments attach to the membrane. This molecular organization suggests that the plasma membrane is divided into at least two functional domains, and appear to provide a mechanism for the strong linkage seen in smooth muscle between Na+/K+ pumping and Na+/Ca2+ exchange, and between Na+/Ca2+ exchange and Ca2+ release from the sarcoplasmic reticulum.

UI MeSH Term Description Entries
D007091 Image Processing, Computer-Assisted A technique of inputting two-dimensional or three-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer. Biomedical Image Processing,Computer-Assisted Image Processing,Digital Image Processing,Image Analysis, Computer-Assisted,Image Reconstruction,Medical Image Processing,Analysis, Computer-Assisted Image,Computer-Assisted Image Analysis,Computer Assisted Image Analysis,Computer Assisted Image Processing,Computer-Assisted Image Analyses,Image Analyses, Computer-Assisted,Image Analysis, Computer Assisted,Image Processing, Biomedical,Image Processing, Computer Assisted,Image Processing, Digital,Image Processing, Medical,Image Processings, Medical,Image Reconstructions,Medical Image Processings,Processing, Biomedical Image,Processing, Digital Image,Processing, Medical Image,Processings, Digital Image,Processings, Medical Image,Reconstruction, Image,Reconstructions, Image
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D002024 Bufo marinus A species of the true toads, Bufonidae, becoming fairly common in the southern United States and almost pantropical. The secretions from the skin glands of this species are very toxic to animals. Rhinella marina,Toad, Giant,Toad, Marine,Giant Toad,Giant Toads,Marine Toad,Marine Toads,Toads, Giant,Toads, Marine
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002155 Calsequestrin Acidic protein found in SARCOPLASMIC RETICULUM that binds calcium to the extent of 700-900 nmoles/mg. It plays the role of sequestering calcium transported to the interior of the intracellular vesicle.
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
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
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

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