Modelling the electrophysiological endothelial cell response to bradykinin

The goal of the present study is to construct a biophysical model of the coronary artery endothelial cell response to bradykinin. This model takes into account intracellular Ca2+ dynamics, membrane potential, a non-selective cation channel, and two Ca2+-dependent K+ channels, as well as intra- and extracellular Ca2+ sources. The model reproduces the experimental data available, and predicts certain quantities which would be hard to obtain experimentally, like the individual K+ channel currents when the membrane potential is allowed to freely evolve, the implication of epoxyeicosatrienoic acids (EETs), and the total K+ released during stimulation. The main results are: (1) the large-conductance K+ channel participates only very little in the overall response; (2) EETs are required in order to explain the experimental current-potential relationships, but are not an essential component of the bradykinin response; and (3) the total K+ released during stimulation gives rise to a concentration in the intercellular space which is of millimolar order. This concentration change is compatible with the hypothesis that K+ contributes to the endothelium-derived hyperpolarizing factor phenomeno

Modelling the electrophysiological endothelial cell response to bradykinin

The goal of the present study is to construct a biophysical model of the coronary artery endothelial cell response to bradykinin. This model takes into account intracellular Ca2+ dynamics, membrane potential, a non-selective cation channel, and two Ca(2+)-dependent K+ channels, as well as intra- and extracellular Ca2+ sources. The model reproduces the experimental data available, and predicts certain quantities which would be hard to obtain experimentally, like the individual K+ channel currents when the membrane potential is allowed to freely evolve, the implication of epoxyeicosatrienoic acids (EETs), and the total K+ released during stimulation. The main results are: (1) the large-conductance K+ channel participates only very little in the overall response; (2) EETs are required in order to explain the experimental current-potential relationships, but are not an essential component of the bradykinin response; and (3) the total K+ released during stimulation gives rise to a concentration in the intercellular space which is of millimolar order. This concentration change is compatible with the hypothesis that K+ contributes to the endothelium-derived hyperpolarizing factor phenomenon

Identification and functional response of interstitial Cajal-like cells from rat mesenteric artery

Cells with irregular shapes, numerous long thin filaments, and morphological similarities to the gastrointestinal interstitial cells of Cajal (ICCs) have been observed in the wall of some blood vessels. These ICC-like cells (ICC-LCs) do not correspond to the other cell types present in the arterial wall: smooth muscle cells (SMCs), endothelial cells, fibroblasts, inflammatory cells, or pericytes. However, no clear physiological role has as yet been determined for ICC-LCs in the vascular wall. The aim of this study has been to identify and characterize the functional response of ICC-LCs in rat mesenteric arteries. We have observed ICC-LCs and identified them morphologically and histologically in three different environments: isolated artery, freshly dispersed cells, and primary-cultured cells from the arterial wall. Like ICCs but unlike SMCs, ICC-LCs are positively stained by methylene blue. Cells morphologically resembling methylene-blue-positive cells are also positive for the ICC and ICC-LC markers α-smooth muscle actin and desmin. Furthermore, the higher expression of vimentin in ICC-LCs compared with SMCs allows a clear discrimination between these two cell types. At the functional level, the differences observed in the variations of cytosolic free calcium concentration of freshly dispersed SMCs and ICC-LCs in response to a panel of vasoactive molecules show that ICC-LCs, unlike SMCs, do not respond to exogenous ATP and [Arginine]8-vasopressi

Recruitment of smooth muscle cells and arterial vasomotion

Investigating the recruitment and synchronization of smooth muscle cells (SMCs) is the key to understanding the physical mechanisms leading to contraction and spontaneous diameter oscillations of arteries, called vasomotion. We improved a method that allows the correlation of calcium oscillations (flashing) of individual SMCs with mean calcium variations and arterial contraction using confocal microscopy. Endothelium-stripped rat mesenteric arteries were cut open, loaded with dual calcium fluorescence probes, and stimulated by increasing concentrations of the vasoconstrictors phenylephrine (PE) and KCl. We found that the number and synchronization of flashing cells depends on vasoconstrictor concentration. At low vasoconstrictor concentration, few cells flash asynchronously and no local contraction is detected. At medium concentration, recruitment of cells is complete and synchronous, leading to strip contraction after KCl stimulation and to vasomotion after PE stimulation. High concentration of PE leads to synchronous calcium oscillations and fully contracted vessels, whereas high concentration of KCl leads to a sustained nonoscillating increase of calcium and to fully contracted vessels. We conclude that the number of simultaneously recruited cells is an important factor in controlling rat mesenteric artery contraction and vasomotion

Structural effects of OH Þ F substitution in trioctahedral micas of the system K2O-FeO-Fe2O3-Al2O3-SiO2-H2O-HF.

The OH => F Substitution in trioctahedral ferrous micas has been investigated at 720 °C. 1 kbar PH2o- under /02conditions set by the MW (FeiOj-Fe^O) buffer.The starting compositions belong to the annite-siderophyllite join:K(Fe-, xAlx)(Si3.xAlUx)01(,(OH): with x 0 (annite). 0.5 (Fe-eastonile). and 0.75 (Es). In F-bearing system. thecompositions investigated belong to (OH.F)-annite. (OH.F)-Fe-eastonile and (OH.F)-Es joins. A single mica phase wasobserved lor (OH.F)-annite in 0 F Substitution induces local cationic changes and consequently a dimensional adaptation of sheets (limitedin such micas to a 5.5°). which in turn conlrols the fluorine solubility in these studied micas. The results alsoshow lhat the Fe-'*/Fe,„Ia| ratio in F-bearing micas is not only controlled by /02 but also by structural constraints.Thefluorine content of natura] biotiles has to be taken into aecount to cslimate oxygen fugacities prevailing in the rocks

Fe-F and Al-F avoidance rule in ferrous-aluminous (OF, F) biotites.

International audienceThe results of infrared and Raman spectroscopic investigations in the OH-slrelching and lattiee-mode regions in synthetic ferrous-aluminous (OH.F)-biotites are presented. In the OH-stretching region (3800-3200 cm '). all micas studied present a high intensity peak at high frequencies [3669 cm ' for (OH)-annite and 3641 cm-' for (OH)-Es] which can be decomposed into two bands and a low intensity peak at low frequencies [3535 er1 for (OH)-annite and 3589 cm ' lor (OH)-Es] which suggests rather a vacant octahedral site. Along the (OH.F)-annite join. the intense peak at 3669 cm ' shifts to lower frequencies as XF increases from 0 to 0.4. In contrast. this peak shifts to higher frequencies along the (OH.F)-Es join (Es K(Fe:25Al())(Si225Al,75)Ol()(OH.F)2). The low-intensity V-band re¬ mains roughly unchanged. The two bands that compose the 3669 cm ' peak are assigned to a N-band resulting from OH-Fe2+Fe2+Fe2+ (Tri-6p vibrations and a Ib-band due to OH-Fe2*Fe2+AP* (Tri-7-) vibrations. As the amount of fluorine increases in micas of the (OH.F)-annite join. the N-band frequency varies weakly but its intensity decreases significantly, while the Ibband becomes more intense. In contrast, these two bands show an opposite behaviour in (OH.F)-Es micas. TTie Nband intensity increases whereas that of the Ib-band decreases. The opposite evolution of the two main bands in the OH-stretching region shows that F is preferentially linked to Fe rather than to AI in (OH.F)-anmte, whereas F is preferentially linked to AI rather than to Fe in (OH.F)-Es. Conse¬ quently. the bond strengths Al-F or Fe-F are not controlled by the Fe-F or Al-F avoidance rule (which would predict lhat fluorine is preferentially associated to Fe in all micas). but by structural constraints. The Al-F or Fe-F avoidance rule may not play a determining role on the fluorine content of the micas as it is generally agrecd.The maximum fluorine contents in micas mainly depend on the ability of the dimensional adaptation of tetrahedral and octahedral layers

An evaluation of potassium ions as endothelium-derived hyperpolarizing factor in porcine coronary arteries

1. In the rat hepatic artery, the endothelium-derived hyperpolarizing factor (EDHF) was identified as potassium. Potassium hyperpolarizes the smooth muscles by gating inward rectified potassium channels and by activating the sodium-potassium adenosine triphosphatase (Na(+)-K(+)ATPase). Our goal was to examine whether potassium could explain the EDHF in porcine coronary arteries. 2. On coronary strips, the inhibition of calcium-dependent potassium channels with 100 nM apamin plus 100 μM charibdotoxin inhibited the endothelium-dependent relaxations, produced by 10 nM substance P and 300 nM bradykinin and resistant to nitro-L-arginine and indomethacin. 3. The scavenging of potassium with 2 mM Kryptofix 2.2.2 abolished the endothelium-dependent relaxations produced by the kinins and resistant to nitro-L-arginine and indomethacin. 4. Forty μM 18α glycyrrethinic acid or 50 μM palmitoleic acid, both uncoupling agents, did not inhibit these kinin relaxations. Therefore, EDHF does not result from an electrotonic spreading of an endothelial hyperpolarization. 5. Barium (0.3 nM) did not inhibit the kinin relaxations resistant to nitro-L-arginine and indomethacin. Therefore, EDHF does not result from the activation of inward rectified potassium channels. 6. Five hundred nM ouabain abolished the endothelium-dependent relaxations resistant to nitro-L-arginine and indomethacin without inhibiting the endothelium-derived NO relaxation. 7. The perifusion of a medium supplemented with potassium depolarized and contracted a coronary strip; however, the short application of potassium hyperpolarized the smooth muscles. 8. These results are compatible with the concept that, in porcine coronary artery, the EDHF is potassium released by the endothelial cells and that this ion hyperpolarizes and relaxes the smooth muscles by activating the Na(+)-K(+)ATPase