Ankyrin-B coordinates the Na/K ATPase, Na/Ca exchanger, and InsP3 receptor in a cardiac T-tubule/SR microdomain.

Published

Journal Article

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 InsP3 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 [Ca2+]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 Ca2+ modulation.

Full Text

Duke Authors

Cited Authors

  • Mohler, PJ; Davis, JQ; Bennett, V

Published Date

  • December 2005

Published In

Volume / Issue

  • 3 / 12

Start / End Page

  • e423 -

PubMed ID

  • 16292983

Pubmed Central ID

  • 16292983

Electronic International Standard Serial Number (EISSN)

  • 1545-7885

International Standard Serial Number (ISSN)

  • 1544-9173

Digital Object Identifier (DOI)

  • 10.1371/journal.pbio.0030423

Language

  • eng