ABSTRACT
Endothel ium-dependent vascular relaxations observed in the presence o f inhibi tors o f ni tr ic oxide ( N O ) and pros tanoid synthesis are widely attributed to an endothel iumderived hyperpolar iz ing factor ( E D H F ) . A l t h o u g h the existence o f E D H F has been demonstrated i n cascade bioassay ( M o m b o u l i et al, 1996), and i n ' sandwich ' strip preparations (Hutcheson et al, 1999), i n rabbit arteries and veins there is evidence that this factor no rmal ly transfers f rom endothel ium to smooth muscle v ia myoendothel ia l gap junct ions fo l lowing s t imulat ion by agonists such as acetylcholine, rather than the extracellular space (Chaytor et al, 1998; D o r a et al, 1999; Y a m a m o t o et al, 1999; Gr i f f i t h and Tay lo r , 1999). G a p junct ions are formed by two inter locked hemi channels or connexons, wh ich are contr ibuted by coupled cells, wi th each connexon
Heterogeneity of EDHF-type relaxations of rabbit and rat arteries 63 constructed f rom six transmembrane protein subunits called connexins that cross the cell membrane four times wi th two loops exposed extracellularly ( K u m a r and G i l u l a , 1996). Interdigitat ion o f these extracellular loops, fo l lowed by a 30° rotat ion, results i n channel dock ing and the format ion o f an aqueous central pore (Perkins et al, 1998). Clusters o f up to several hundred ind iv idua l gap junct ions i n plaque-l ike structures permit the direct intercellular transfer o f ions and molecules smaller than 1 k D a i n size at local ized sites in the cell membrane (Bukauskas et al, 2000). A t least 20 connexin (Cx) subtypes have been identified in m a m m a l i a n tissues and these are convent ional ly classified according to their molecular weight i n k D a wi th endothelial and vascular smooth muscle cells var iably expressing C x 3 7 , C x 4 0 and Cx43 according to species and vessel type (Carter et al, 1996; B r i n k , 1998; van K e m p e n and Jongsma, 1999). In theory, myoendothel ia l gap junct ions cou ld thus conta in homotyp ic channels i n wh ich each contr ibut ing connexon is constructed f rom the same connexin subtype (e.g., Cx43 /Cx43) , heterotypic channels i n wh ich each connexon is constructed f rom a different subtype (e.g., Cx37 /Cx43) and heteromeric channels i n wh ich each connexon contains a mixture o f different connexin proteins.
