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Ankyrin-B Coordinates the Na/K ATPase, Na/Ca Exchanger, and InsP(3) Receptor in a Cardiac T-Tubule/SR Microdomain

We report identification of an ankyrin-B-based macromolecular complex of Na/K ATPase (alpha 1 and alpha 2 isoforms), Na/Ca exchanger 1, and InsP(3) receptor that is localized in cardiomyocyte T-tubules in discrete microdomains distinct from classic dihydropyridine receptor/ryanodine receptor “dyads....

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Detalles Bibliográficos
Autores principales: Mohler, Peter J, Davis, Jonathan Q, Bennett, Vann
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287507/
https://www.ncbi.nlm.nih.gov/pubmed/16292983
http://dx.doi.org/10.1371/journal.pbio.0030423
Descripción
Sumario:We report identification of an ankyrin-B-based macromolecular complex of Na/K ATPase (alpha 1 and alpha 2 isoforms), Na/Ca exchanger 1, and InsP(3) receptor that is localized in cardiomyocyte T-tubules in discrete microdomains distinct from classic dihydropyridine receptor/ryanodine receptor “dyads.” E1425G mutation of ankyrin-B, which causes human cardiac arrhythmia, also blocks binding of ankyrin-B to all three components of the complex. The ankyrin-B complex is markedly reduced in adult ankyrin-B(+/−) cardiomyocytes, which may explain elevated [Ca(2+)](i) transients in these cells. Thus, loss of the ankyrin-B complex provides a molecular basis for cardiac arrhythmia in humans and mice. T-tubule-associated ankyrin-B, Na/Ca exchanger, and Na/K ATPase are not present in skeletal muscle, where ankyrin-B is expressed at 10-fold lower levels than in heart. Ankyrin-B also is not abundantly expressed in smooth muscle. We propose that the ankyrin-B-based complex is a specialized adaptation of cardiomyocytes with a role for cytosolic Ca(2+) modulation.