ABSTRACT:In the vessel walls, the connective tissue components surrounding the smooth muscle cells display a high binding capacity for small cations which has been ascribed to the presence of polyanionic proteoglycans. 23 Na+ and 3 91<.+ NMR measurements indicate that, while monovalent cations exert merely competitive interaction, divalent cations induce a conformational transition changing specifically the affinities for other ion species. Mg 2 + or Ca 2 + ions cause such a configurational change in the physiologic concentration range which promotes allosteric, cooperative binding ofK+ or Na+ ions, respectively, to vascular connective tissue. The geometry of narrow tissue clefts in the interstitial compartment of the vessel wall entails that an increase of extracellular Mg 2 + (Ca 2 +) concentration effects a decrease of external K+ (Na+) concentration in the vicinity of vascular smooth muscle cell membranes. Membrane hyperpolarization and vasorelaxation is the result.Proteoglycans are viscoelastic, anionic biopolyelectrolytes which consist of many highly sulphated and carboxylated glycosaminoglycan chains that are covalently attached to the protein core. The physicochemical and functional properties of the proteoglycans are due to the fact that in solution they are strongly hydrated anionic macromolecules. With an external strain, such a compound can go from a randomly coiled to an oriented state.The intensity of the blood flow can cause such a conformational transition of proteoheparan sulphate, integrated in the membrane of smooth muscle and endothelial cells. This conformational change is combined with an increase in binding sites for Na+ ions. When flow is reduced, inner molecular, elastic recoil forces guarantee entropic coiling. Sodium ions are released into the solution.Heparan sulphate shows Ca 2 + -dependent conformational transitions. These transitions are correlated with an increased or decreased local mobility of the molecular chains as the correlation times prove. Between 1 and 2.5 mmol/1 [Ca 2 +]0 , not only are Ca 2 + ions bound but Na+ ions are also bound in an allosteric, cooperative manner. Above 2.5 mmol/1 [Ca 2 +]0 , there is a competitive expulsion of Na+ ions from their binding sites on the heparan sulphate by Ca 2 + ions. These findings support the hypothesis that proteoglycans, integrated in the cell membrane, fulfill the mechano-chemical requirements of a flow sensor. KEY WORDS: Anionic Biopolymers / Heparan Sulphate/ Cation Binding/ 23 Na+ NMR Studies / Conformational Changes / Viscoelasticity / Blood Flow Sensor Macromolecular polyelectrolytes play a decisive part in the control of transmembrane mass transport and cellular information on both sides of the cell membrane. Thus, there is an urgent need for a more integrated approach towards systematically evaluating the structure and function of cytoskeletal proteins and their interactions with the extracellular matrix in membrane biophysics 697
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