Glutamate transporter control of ambient glutamate levels

Accurate knowledge of the ambient extracellular glutamate concentration in brain is required for understanding its potential impacts on tonic and phasic receptor signaling. Estimates of ambient glutamate based on microdialysis measurements are generally in the range of ∼2–10 μM, approximately 100-fold higher than estimates based on electrophysiological measurements of tonic NMDA receptor activity (∼25–90 nM). The latter estimates are closer to the low nanomolar estimated thermodynamic limit of glutamate transporters. The reasons for this discrepancy are not known, but it has been suggested that microdialysis measurements could overestimate ambient extracellular glutamate because of reduced glutamate transporter activity in a region of metabolically impaired neuropil adjacent to the dialysis probe. We explored this issue by measuring diffusion gradients created by varying membrane densities of glutamate transporters expressed in Xenopus oocytes. With free diffusion from a pseudo-infinite 10 μM glutamate source, the surface concentration of glutamate depended on transporter density and was reduced over 2 orders of magnitude by transporters expressed at membrane densities similar to those previously reported in hippocampus. We created a diffusion model to simulate the effect of transport impairment on microdialysis measurements with boundary conditions corresponding to a 100 μm radius probe. A gradient of metabolic disruption in a thin (∼100 μm) region of neuropil adjacent to the probe increased predicted [Glu] in the dialysate over 100-fold. The results provide support for electrophysiological estimates of submicromolar ambient extracellular [Glu] in brain and provide a possible explanation for the higher values reported using microdialysis approaches

Resonant cavity enhanced detectors embedded in photonic crystals

Cataloged from PDF version of article.We report a resonant cavity enhanced (RCE) detector built around a three-dimensional photonic band gap crystal. The RCE detector was built by placing a monopole antenna within the localized modes of planar and boxlike defectstructures. The enhanced electric field around these defectstructures were then measured by a microwave detector and a network analyzer. We measured a power enhancement factor of 3450 for planar cavity structures. A Fabry–Perot cavity model was used to understand and predict resonant cavity enhancement in this structure. The tuning bandwidth of the RCE detector extends from 10.5 to 12.8 GHz, which corresponds to the full photonic band gap by the crystal. These RCE detectors have increased sensitivity and efficiency when compared to conventional detectors, and can be used for various applications. © 1998 American Institute of Physic

Effect of afterload alterations on the functional border zone measured with two-dimensional echocardiography during acute coronary occlusion

In the setting of acute myocardial infarction, pharmacologic intervention resulting in afterload changes are common but the effect of these changes on regional left ventricular function, and specifically the functional border zone, has not been fully investigated. Accordingly, we studied the effects of afterload manipulation on circumferential flow-function relationships and the functional border zone in 16 open-chest, anesthetized dogs. During left circumflex coronary artery occlusion, eight animals were infused with phenylephrine to increase afterload; eight others received nitroprusside for afterload reduction. Following coronary artery occlusion, subendocardial blood flow and wall thickening decreased in the ischemic zone (p p = ns). Similarly, when blood pressure was increased by 47%, the extent of the functional border zone did not change (32 +/- 10 degrees vs 37 +/- 10 degrees). Therefore circumferential flow-function relations and the spatial extent of the functional border zone are not altered by changing afterload during acute left circumflex coronary artery occlusion in this model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27132/1/0000125.pd

Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD) decreased the levels of free carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC: FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD

Regional metabolism during coronary occlusion, reperfusion, and reocclusion using phosphorus31 nuclear magnetic resonance spectroscopy in the intact rabbit,

Few studies have examined metabolic consequences of coronary occlusion and reperfusion using phosphorus31 nuclear magnetic resonance (31P-NMR) in an intact animal model. Accordingly, we developed a model to study serial changes in myocardial metabolism in the intact open-chest rabbit. Ten animals underwent 20 +/- 2 minutes of regional coronary occlusion and 60 +/- 10 minutes of reperfusion followed by reocclusion. Cardiac-gated 31P-NMR spectra were obtained with a regional surface coll over the ischemic area during baseline, occlusion, reperfusion, and reocclusion conditions. Phosphocreatine fell with both the initial and second ischemic insults to 65% +/- 5% of baseline for the first occlusion (p p = 0.07), with normal levels reattained in the intervening period of reperfusion (99% +/- 5% of baseline, p = NS). Concordant inverse changes were seen with inorganic phosphates. At occlusion levels of inorganic phosphates were 135% +/- 10% of baseline (p p p p p p = NS). We conclude that reperfusion restores levels of phosphocreatine and adenosine triphosphate while returning levels of inorganic phosphates to baseline. Deleterious changes in high-energy phosphate metabolism are not potentiated by reocclusion in this model. 31P-NMR spectroscopy holds promise as a technique to noninvasively monitor intracellular biochemical processes serially during various interventions in the intact animal model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28117/1/0000566.pd