Connexin expression and turnover - Implications for cardiac excitability

Electrical activation of the heart requires current transfer from one cell to another via gap junctions, arrays of densely packed intercellular channe ls. The extent to which cardiac myocytes are coupled is determined by multi ple mechanisms, including tissue-specific patterns of expression of diverse gap junction channel proteins (connexins), and regulatory pathways that co ntrol 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 he art suggest that connexin43, the principal cardiac connexin, is surprisingl y short-lived (half-life approximate to 1.3 hours). Both the proteasome and the lysosome participate in connexin43 degradation. Other ion channel prot eins, such as those forming selected voltage-gated K+ channels, may also ex hibit rapid turnover kinetics. Regulation of connexin degradation may be an important mechanism for adjusting intercellular coupling in the heart unde r normal and pathophysiological conditions.