Gap Junctions and Connexin Expression in Human Heart Disease

摘要: Sequential contraction of the cardiac chambers depends on orderly spread wave electrical excitation from one cardiomyocyte to next, throughout heart. As discussed in earlier chapters this volume, pathways enabling cell-to-cell current flow are formed by gap junctions that link individual cardiomyocytes into a functional syncytium. Gap essentially clusters transmembrane channels span paired plasma membranes neighboring cells, linking their cytoplasmic compartments together form for direct communication. The component proteins gap-junctional channel, connexins, assembled hexamers which hemi-channels termed connexons, complete channel being docking pair connexons across adjacent membranes. Twenty different connexin genes have now been identified human (Willecke et al., 2001), and most tissues, including those cardiovascular system, express two or more isoforms. Three principal isoforms — connexin43, connexin40 connexin45 expressed (reviews, Beyer 1997; Severs, 1999; Severs further such as connexin46 (Paul 1991) connexin57 (Manthey 1999) may also be present trace amounts. Gapjunctional composed connexins exhibit distinctive biophysical properties vitro (review, Bruzzone aI., 1996), studies transgenic mice demonstrate precise vivo depend part specific they constructed, though there is considerable capacity compensation isoform another (Kirchhoff 2000; KrUger Plum Tamaddon van ijen 2001). Different subsets combinations relative quantities 43, 40 45, potentially providing regional differentiation electrophysiological properties. concept has thus developed junction organization spatially defined patterns expression preside over precisely chestrated govern normal heart rhythm.