K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

<p>Abstract</p> <p>Background</p> <p>Lung epithelial Na⁺channels (ENaC) are regulated by cell Ca²⁺signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K⁺channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K⁺channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC) by up-regulating both apical and basolateral ion transport.</p> <p>Methods</p> <p>Verapamil-induced depression of heterologously expressed human αβγ ENaC in <it>Xenopus </it>oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441), and <it>in vivo </it>alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca²⁺signal in H441 cells was analyzed using Fluo 4AM.</p> <p>Results</p> <p>The rate of <it>in vivo </it>AFC was reduced significantly (40.6 ± 6.3% of control, <it>P </it>< 0.05, n = 12) in mice intratracheally administrated verapamil. K_Ca3.1(1-EBIO) and K_ATP(minoxidil) channel openers significantly recovered AFC. In addition to short-circuit current (Isc) in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca²⁺signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca²⁺in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, K_V(pyrithione-Na), K _Ca3.1(1-EBIO), and K_ATP(minoxidil) channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na⁺and K⁺transport pathways.</p> <p>Conclusions</p> <p>Our observations demonstrate that K⁺channel openers are capable of rescuing reduced vectorial Na⁺transport across lung epithelial cells with impaired Ca²⁺signal.</p

Combining farmers' decision rules and landscape stochastic regularities for landscape modelling

International audienceLandscape spatial organization (LSO) strongly impacts many environmental issues. Modelling agricultural landscapes and describing meaningful landscape patterns are thus regarded as key-issues for designing sustainable landscapes. Agricultural landscapes are mostly designed by farmers. Their decisions dealing with crop choices and crop allocation to land can be generic and result in landscape regularities, which determine LSO. This paper comes within the emerging discipline called "landscape agronomy", aiming at studying the organization of farming practices at the landscape scale. We here aim at articulating the farm and the landscape scales for landscape modelling. To do so, we develop an original approach consisting in the combination of two methods used separately so far: the identification of explicit farmer decision rules through on-farm surveys methods and the identification of landscape stochastic regularities through data-mining. We applied this approach to the Niort plain landscape in France. Results show that generic farmer decision rules dealing with sunflower or maize area and location within landscapes are consistent with spatiotemporal regularities identified at the landscape scale. It results in a segmentation of the landscape, based on both its spatial and temporal organization and partly explained by generic farmer decision rules. This consistency between results points out that the two modelling methods aid one another for land-use modelling at landscape scale and for understanding the driving forces of its spatial organization. Despite some remaining challenges, our study in landscape agronomy accounts for both spatial and temporal dimensions of crop allocation: it allows the drawing of new spatial patterns coherent with land-use dynamics at the landscape scale, which improves the links to the scale of ecological processes and therefore contributes to landscape ecology.L'organisation du paysage influe sur les problèmes environnementaux. Modéliser les paysages pour les décrire à l'aide de formes significatives est une étage clé. Les paysages agricoles sont principalement construits par les agriculteurs dont les décision d'assolement peuvent être génériques et déterminer des régularités dans l'organisation du paysage. Cet article contribue à l'agronomie des paysage qui est une discipline émergente. Nous cherchons à articuler les échelles du paysage et de l'exploitation agricole en développant deux méthodes : l'une consiste à identifier les décisions des agriculteurs par le bais d'enquêtes, l'autre consiste à retrouver des régularités stochastiques dans le paysage par le bais de fouille de données. Nous avons appliqué cette approche au paysage de la plaine de Niort en France. Les résultats montrent que les décisions des agriculteurs en matière de tournesol et maïs sont génériques et ont des effets sur le paysages que des méthodes de fouille de données révèlent et quantifient

4,4-Diphenyl-1-propyl-2-propylsulfanyl-4,5-dihydro-1H-imidazol-5-one

In the title molecule, C21H24N2OS, the five-membered ring is planar with an r.m.s. deviation of 0.0142 Å. The phenyl rings are inclined to the plane of the dihydroimidazolone ring by 60.81 (6) and 79.23 (6)°. In the crystal, inversion dimers are formed by a C—H...O hydrogen bond and a C—H...π(ring) interaction. Additional C—H...O hydrogen bonds and C—H...π(ring) interactions connect these dimers into chains along the c-axis direction