Gap Junctions in the Vasculature The essence of cardiovascular function is cellular coordination
Gap Junctions in the Vasculature The essence of cardiovascular function is cellular coordination
Pathway for cell-cell communication -Autocrine and paracrine PG,ET,NO -Gap junction Electric charge,small signaling molecules
Pathway for cell-cell communication ▪ Autocrine and paracrine ▪ PG, ET, NO ▪ Gap junction ▪ Electric charge, small signaling molecules
Gap junction A functional gap junction Gap junctional intercellular communication 2 opposing hexamer (connexon,hemichannel) 6 connexin proteins
Gap junction ▪ A functional gap junction ▪ 2 opposing hexamer (connexon, hemichannel): ▪ 6 connexin proteins
Vascular Gap Junction ■Role -Uniting SM and endothelium -Providing the pathway for the radial and longitudinal communication -Form a syncytium,the smooth muscle endothelial cell unit
Vascular Gap Junction ▪ Role ▪ Uniting SM and endothelium ▪ Providing the pathway for the radial and longitudinal communication ▪ Form a syncytium, the smooth muscle - endothelial cell unit
Vascular Gap Junction ■Research methods Specific and selective gap junction inhibitors -Traditional inhibitors:nonspecific Halothane,octanol,glycyrrhizic acid metabolites Gap-junctional blocking peptide -Glycoconjugate:a specific connexon blockade Cell-specific gap junction knockout mice
Vascular Gap Junction ▪ Research methods ▪ Specific and selective gap junction inhibitors ▪ Traditional inhibitors: nonspecific ▪ Halothane, octanol, glycyrrhizic acid metabolites ▪ Gap-junctional blocking peptide ▪ Glycoconjugate: a specific connexon blockade ▪ Cell-specific gap junction knockout mice
Vascular Gap Junction Electron microscopy -Gap junctional plaque (endothelium) -Dye movement between adjacent cells A ▣Electrical coupling
Vascular Gap Junction ▪ Electron microscopy ▪ Gap junctional plaque (endothelium) ▪ Dye movement between adjacent cells ▪ Electrical coupling
Myoendothelial junction (MEJ) -Gap junction located at the smooth muscle- endothelial cell interface
Myoendothelial junction (MEJ) ▪ Gap junction located at the smooth muscleendothelial cell interface
Myoendothelial junction (MEJ) -Movement of current -Movement of signaling molecule ▣Ca2+,IP3
Myoendothelial junction (MEJ) ▪ Movement of current ▪ Movement of signaling molecule ▪ Ca2+, IP3
Coupling between the smooth muscle and endothelium ▣↑SMC Ca2+→MEJ→endothelial cell Ca2+↑ Changes in SM membrane potential -MEJ -gating of voltage-sensitive Ca2+channels in the endothelial cell EDHf→MEJ>electrical signal→SM
Coupling between the smooth muscle and endothelium ▪ SMC Ca2+→MEJ → endothelial cell Ca2+ ▪ Changes in SM membrane potential →MEJ → gating of voltage-sensitive Ca2+ channels in the endothelial cell ▪ EDHF →MEJ → electrical signal →SM
