Both volatile and intravenous general anesthetics allosterically enhance gamma-aminobutyric acid (GABA)-evoked chloride currents at the GABA type A (GABAA) receptor. Recent work has revealed that two specific amino acid residues within transmembrane domain (TM)2 and TM3 are necessary for positive modulation of GABAA and glycine receptors by the volatile anesthetic enflurane. We now report that mutation of these residues within either GABAA alpha2 (S270 or A291) or beta1 (S265 or M286) subunits resulted in receptors that retain normal or near-normal gating by GABA but are insensitive to clinically relevant concentrations of another inhaled anesthetic, isoflurane. To determine whether receptor modulation by intravenous general anesthetics also was affected by these point mutations, we examined the effects of propofol, etomidate, the barbiturate methohexital, and the steroid alphaxalone on wild-type and mutant GABAA receptors expressed in human embryonic kidney 293 cells. In most cases, these mutations had little or no effect on the actions of these intravenous anesthetics. However, a point mutation in the beta1 subunit (M286W) abolished potentiation of GABA by propofol but did not alter direct activation of the receptor by high concentrations of propofol. These data indicate that the receptor structural requirements for positive modulation by volatile and intravenous general anesthetics may be quite distinct.
Isolated internodes of Chara corallina have been used to study the gating of aquaporins (water channels) in the presence of high concentrations of osmotic solutes of different size (molecular weight). Osmolytes were acetone and three glycol ethers: ethylene glycol monomethyl ether (EGMME), diethylene glycol monomethyl ether (DEGMME), and triethylene glycol monoethyl ether (TEGMEE). The 'osmotic efficiency' of osmolytes was quite different. Their reflection coefficients ranged between 0.15 (acetone), 0.59 (EGMME), 0.78 (DEGMME), and 0.80 (TEGMEE). Bulk water permeability (Lp) and diffusive permeabilities (Ps) of heavy water (HDO), hydrogen peroxide (H2O2), acetone, and glycol ethers (EGMME, DEGMME, and TEGMEE) were measured using a cell pressure probe. Cells were treated with different concentrations of osmotic solutes of up to 800 mM ( approximately 2.0 MPa of osmotic pressure). Inhibition of aquaporin activity increased with both increasing concentration and size of solutes (reflection coefficients). As cell Lp decreased, Ps increased, indicating that water and solutes used different passages across the plasma membrane. Similar to earlier findings of an osmotic gating of ion channels, a cohesion/tension model of the gating of water channels in Chara internodes by high concentration is proposed. According to the model, tensions (negative pressures) within water channels affected the open/closed state by changing the free energy between states and favoured a distorted/collapsed rather than the open state. They should have differed depending on the concentration and size of solutes that are more or less excluded from aquaporins. The bigger the solute, the lower was the concentration required to induce a reversible closure of aquaporins, as predicted by the model.
Localized primary emissions of carbonaceous aerosol are the major drivers of intracity variability of submicron particulate matter (PM 1 ) concentrations. We investigated spatial variations in PM 1 composition with mobile sampling in Pittsburgh, Pennsylvania, United States and performed sourceapportionment analysis to attribute primary organic aerosol (OA) to traffic (HOA) and cooking OA (COA). In high-source-impact locations, the PM 1 concentration is, on average, 2 μg m −3 (40%) higher than urban background locations. Traffic emissions are the largest source contributing to populationweighted exposures to primary PM. Vehicle-miles traveled (VMT) can be used to reliably predict the concentration of HOA and localized black carbon (BC) in air pollutant spatial models. Restaurant count is a useful but imperfect predictor for COA concentration, likely due to highly variable emissions from individual restaurants. Near-road cooking emissions can be falsely attributed to traffic sources in the absence of PM source apportionment. In Pittsburgh, 28% and 9% of the total population are exposed to >1 μg m −3 of traffic-and cooking-related primary emissions, with some populations impacted by both sources. The source mix in many U.S. cities is similar; thus, we expect similar PM spatial patterns and increased exposure in high-source areas in other cities.
The sessile lifestyle of plants constrains their ability to acquire mobile nutrients such as nitrate. Whereas proliferation of roots might help in the longer term, nitrate-rich patches can shift rapidly with mass flow of water in the soil. A mechanism that allows roots to follow and capture this source of mobile nitrogen would be highly desirable. Here, we report that variation in nitrate concentration around roots induces an immediate alteration of root hydraulic properties such that water is preferentially absorbed from the nitrate-rich patch. Further, we show that this coupling between nitrate availability and water acquisition results from changes in cell membrane hydraulic properties and is directly related to intracellular nitrate concentrations. Split-root experiments in which nitrate was applied to a portion of the root system showed that the response is both localized and reversible, resulting in rapid changes in water uptake to the portions of the roots exposed to the nitrate-rich patch. At the same time, water uptake by roots not supplied with nitrate was reduced. We believe that the increase in root hydraulic conductance in one part causes a decline of water uptake in the other part due to a collapse in the water potential gradient driving uptake. The translation of local information, in this case nitrate concentration, into a hydraulic signal that can be transmitted rapidly throughout the plant and thus coordinate responses at the whole plant level, represents an unexpected, higher level physiological interaction that precedes the level of gene expression.
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