title: Connexin expression and turnover : implications for cardiac excitability.
abstract: Electrical activation of the heart requires current transfer from one cell to another via gap junctions, arrays of densely packed intercellular channels. The extent to which cardiac myocytes are coupled is determined by multiple mechanisms, including tissue-specific patterns of expression of diverse gap junction channel proteins (connexins), and regulatory pathways that control connexin synthesis, intracellular trafficking, assembly into channels, and degradation. Many connexins, including those expressed in the heart, have been found to turn over rapidly. Recent studies in the intact adult heart suggest that connexin43, the principal cardiac connexin, is surprisingly short-lived (half-life approximately 1.3 hours). Both the proteasome and the lysosome participate in connexin43 degradation. Other ion channel proteins, such as those forming selected voltage-gated K(+) channels, may also exhibit rapid turnover kinetics. Regulation of connexin degradation may be an important mechanism for adjusting intercellular coupling in the heart under normal and pathophysiological conditions.
authors.affiliation: Departments of Pathology and Medicine and the Center for Cardiovascular Research, Washington University, St. Louis, MO 63110, USA. saffitz@pathbox.wustl.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Saffitz
authors.forename: J G
authors.initials: JG
authors.lastname: Laing
authors.forename: K A
authors.initials: KA
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000818:Animals; D017630:Connexins / Q000235:genetics* / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D008955:Models, Cardiovascular; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex
chemical_list: D017630:Connexins; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex