Sodium–Calcium Exchanger Can Account for Regenerative Ca2+ Entry in Thin Astrocyte Processes

Calcium transients in thin astrocytic processes can be important in synaptic plasticity, but their mechanism is not completely understood. Clearance of synaptic glutamate leads to increase in astrocytic sodium. This can electrochemically favor the reverse mode of the Na/Ca-exchanger (NCX) and allow calcium into the cell, accounting for activity-dependent calcium transients in perisynaptic astrocytic processes. However, cytosolic sodium and calcium are also allosteric regulators of the NCX, thus adding kinetic constraints on the NCX-mediated fluxes and providing for complexity of the system dynamics. Our modeling indicates that the calcium-dependent activation and also calcium-dependent escape from the sodium-mediated inactive state of the NCX in astrocytes can form a positive feedback loop and lead to regenerative calcium influx. This can result in sodium-dependent amplification of calcium transients from nearby locations or other membrane mechanisms. Prolonged conditions of elevated sodium, for example in ischemia, can also lead to bistability in cytosolic calcium levels, where a delayed transition to the high-calcium state can be triggered by a short calcium transient. These theoretical predictions call for a dedicated experimental estimation of the kinetic parameters of the astrocytic Na/Ca-exchanger

Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia

During hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. Here, we describe a mechanism of brain oxygen sensing that mediates the dilation of intraparenchymal cerebral blood vessels in response to reductions in oxygen supply. In vitro and in vivo experiments conducted in rodent models show that during hypoxia, cortical astrocytes produce the potent vasodilator nitric oxide (NO) via nitrite reduction in mitochondria. Inhibition of mitochondrial respiration mimics, but also occludes, the effect of hypoxia on NO production in astrocytes. Astrocytes display high expression of the molybdenum-cofactor-containing mitochondrial enzyme sulfite oxidase, which can catalyze nitrite reduction in hypoxia. Replacement of molybdenum with tungsten or knockdown of sulfite oxidase expression in astrocytes blocks hypoxia-induced NO production by these glial cells and reduces the cerebrovascular response to hypoxia. These data identify astrocyte mitochondria as brain oxygen sensors that regulate cerebral blood flow during hypoxia via release of nitric oxide

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using Raman microspectroscopy

This paper presents a nonivasive approach to study redox state of reduced cytochromes [Image: see text], [Image: see text] and [Image: see text] of complexes II and III in mitochondria of live cardiomyocytes by means of Raman microspectroscopy. For the first time with the proposed approach we perform studies of rod- and round-shaped cardiomyocytes, representing different morphological and functional states. Raman mapping and cluster analysis reveal that these cardiomyocytes differ in the amounts of reduced cytochromes [Image: see text], [Image: see text] and [Image: see text]. The rod-shaped cardiomyocytes possess uneven distribution of reduced cytochromes [Image: see text], [Image: see text] and [Image: see text] in cell center and periphery. Moreover, by means of Raman spectroscopy we demonstrated the decrease in the relative amounts of reduced cytochromes [Image: see text], [Image: see text] and [Image: see text] in the rod-shaped cardiomyocytes caused by H(2)O(2)-induced oxidative stress before any visible changes. Results of Raman mapping and time-dependent study of reduced cytochromes of complexes II and III and cytochrome [Image: see text] in cardiomyocytes are in a good agreement with our fluorescence indicator studies and other published data

Synchronized renal blood flow dynamics mapped with wavelet analysis of laser speckle flowmetry data

Full-field laser speckle microscopy provides real-time imaging of superficial blood flow rate. Here we apply continuous wavelet transform to time series of speckle-estimated blood flow from each pixel of the images to map synchronous patterns in instantaneous frequency and phase on the surface of rat kidneys. The regulatory mechanism in the renal microcirculation generates oscillations in arterial blood flow at several characteristic frequencies. Our approach to laser speckle image processing allows detection of frequency and phase entrainments, visualization of their patterns, and estimation of the extent of synchronization in renal cortex dynamics

Fluorescent images.

<p>Microphotographs of (A) rod- and (B) round-shaped cardiomyocytes in the reflected light and fluorescent images of the same cells obtained with -sensitive dye rhodamin123 (C) and (D). Increase in the intensity of Rh123 fluorescence corresponds to the decrease in . Color bar shows value of the fluorescence intensity in cps. White rectangles on microphotographs show cell areas where Raman images were recorded. Horizontal length of the rectangles corresponds to 20 m.</p

Raman map analysis.

<p>Raman maps of rod-and round-shaped cardiomyocytes from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041990#pone-0041990-g002" target="_blank">Fig. 2 A</a> showing ratios (A), (B) and (C).</p

Rod- and round-shaped cardiomyocytes.

<p>(A) Microphotographs of rod- and round-shaped cardiomyocytes in the reflected light. White rectangle shows place on microphotographs where clustering and Raman maps shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041990#pone-0041990-g003" target="_blank">Figs. 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041990#pone-0041990-g004" target="_blank">4</a> were recorded. Horizontal length of the rectangle corresponds to 20 m. (B) Raman spectra of the same rod and round-shaped cardiomyocytes recorded from the cell centers. Vertical bar corresponds to the Raman intensity, a.u. Grey dotted vertical lines shows positions of main maxima in cardiomyocyte Raman spectra.</p