Dissection of P2X4 and P2X7 receptor current components in BV-2 microglia

Microglia cells represent the immune system of the central nervous system. They become activated by ATP released from damaged and inflamed tissue via purinergic receptors. Ionotropic purinergic P2X4 and P2X7 receptors have been shown to be involved in neurological inflammation and pain sensation. Whether the two receptors assemble exclusively as homotrimers or also as heterotrimers is still a matter of debate. We investigated the expression of P2X receptors in BV-2 microglia cells applying the whole-cell voltage-clamp technique. We dissected P2X4 and P2X7 receptor-mediated current components by using specific P2X4 and P2X7 receptor blockers and by their characteristic current kinetics. We found that P2X4 and P2X7 receptors are activated independently from each other, indicating that P2X4/P2X7 heteromers are not of functional significance in these cells. The pro-inflammatory mediators lipopolysaccharide and interferon γ, if applied in combination, upregulated P2X4, but not P2X7 receptor-dependent current components also arguing against phenotypically relevant heteromerization of P2X4 and P2X7 receptor subunitsPublikationsfond ML

Characteristics of P2X7 receptors from human B lymphocytes expressed in Xenopus oocytes

AbstractHuman B lymphocytes express an ATP-gated ion channel (P2Z receptor), which shares similarities with the recently identified P2X7 receptor. Using gene specific primers, we have now isolated P2X7 cDNA from the total RNA of human B lymphocytes. This hP2X7 receptor subtype was expressed in Xenopus oocytes and electrophysiologically characterized. The hP2X7 receptor is similar to, but does not completely match, P2Z of human B cells. The hP2X7 receptors resemble the P2Z receptors with regard to the ATP concentration of half maximal activation, reproducibility, permeation characteristics and lack of desensitization of the ATP-evoked currents. However, in contrast to the native lymphocytic P2Z receptor, the time course of activation of hP2X7 displayed an additional linearly increasing current component. Furthermore, a second, small and slowly deactivating current component exists only in hP2X7 expressed in oocytes. The activation and deactivation kinetics as well as permeation characteristics of hP2X7 are different from rat P2X7 recently expressed in oocytes. Unlike in mammalian cells, hP2X7 expressed in Xenopus oocytes is not sufficient to induce large non-selective pores

Network platform for sound information analyzis

A new technique of audio information processing for automatic analysis and classification of records, including speech, has been proposed. The technique is based on information representation in the form of associative semantic (cognitive) network structure and deals with amplitude and frequency layers both

Different K+-release in distal myogenic and neurogenic muscular weakness during non-ischemic exercise

Introduction: In myotonic dystrophy, an increased potassium release upon ischemic forearm exercise has been previously described. However, it remains unclear whether this is specific for myotonic dystrophies or just due to distal muscular weakness. Methods: Non-ischemic forearm test (NIFET) was performed and venous K+ concentration was measured at rest and at three different force levels (20–30%, 50–60%, 70–80%) related to maximal contraction force (MCF) in patients with distal myogenic (n = 7), neurogenic (n = 7) muscular weakness and healthy volunteers (n = 12). The specific K+ release was defined as K+ increase related to workload as force-time-integral during repetitive contraction. Results: Workload was lower at all force levels in both disease groups compared to the control group. With increasing workload, the K+ concentrations increased in all study groups. Analysing individual force levels related to the maximum contraction force (MCF), a higher specific K+ release was measured at low force levels in myopathies (20–30% MCF) in comparison to higher force levels (p = 0.02). At 20–30% MCF, the specific K+ release was significantly higher in myogenic compared to neurogenic muscular weakness (p = 0.005). At 50–60% and 70–80% MCF, the specific K+ values converged and did not significantly differ between the three groups (p = 0.09 and p = 0.37). Discussion: At low force levels, K+ efflux related to workload is higher in patients with myogenic in comparison to neurogenic distal paresis. Our results indicate a different regulation of K+ balance in neurogenic and myogenic muscular weakness possibly due to a different recruitment behaviour of motor units and the firing rate of motor neurons.Publikationsfonds ML

The Milky Way Nuclear Star Cluster

In the center of the Milky Way, as well as in many other galaxies, a compact star cluster around a very massive black hole is observed. One of the possible explanations for the formation of such Nuclear Star Clusters is based on the 'merging' of globular clusters in the inner galactic potential well. By mean of sophisticated N-body simulations, we checked the validity of this hypothesis and found that it may actually has been the one leading to the formation of the Milky Way Nuclear Star Cluster.Comment: 4 pages, 2 figures, proceedings of "Stellar Clusters and Associations - A RIA workshop on GAIA", 23-27 May 2011, Granada, Spai

The Herschel Exploitation of Local Galaxy Andromeda (HELGA). VI. The distribution and properties of molecular cloud associations in M31

In this paper we present a catalog of Giant Molecular Clouds (GMCs) in the An- dromeda (M31) galaxy extracted from the Herschel Exploitation of Local Galaxy An- dromeda (HELGA) dataset. GMCs are identified from the Herschel maps using a hierarchical source extraction algorithm. We present the results of this new catalog and characterise the spatial distribution and spectral energy properties of its clouds based on the radial dust/gas properties found by Smith et al (2012). 326 GMCs in the mass range 104 − 107 M⊙ are identified, their cumulative mass distribution is found to be proportional to M −2.34 in agreement with earlier studies. The GMCs appear to follow the same cloud mass to LCO correlation observed in the Milky Way. However, comparison between this catalog and interferometry studies also shows that the GMCs are substructured below the Herschel resolution limit suggesting that we are observing associations of GMCs. Following Gordon et al. (2006), we study the spatial structure of M31 by splitting the observed structure into a set of spiral arms and offset rings. We fit radii of 10.3 and 15.5 kpc to the two most prominent rings. We then fit a logarithmic spiral with a pitch angle of 8fdg9 to the GMCs not associated with either ring. Last, we comment on the effects of deprojection on our results and investigate the effect different models for M31's inclination will have on the projection of an unperturbed spiral arm system

The Herschel Virgo Cluster Survey: VI. The far-infrared view of M87

The origin of the far-infrared emission from the nearby radio galaxy M87 remains a matter of debate. Some studies find evidence of a far-infrared excess due to thermal dust emission, whereas others propose that the far-infrared emission can be explained by synchrotron emission without the need for an additional dust emission component. We present Herschel PACS and SPIRE observations of M87, taken as part of the science demonstration phase observations of the Herschel Virgo Cluster Survey. We compare these data with a synchrotron model based on mid-infrared, far-infrared, submm and radio data from the literature to investigate the origin of the far-infrared emission. Both the integrated SED and the Herschel surface brightness maps are adequately explained by synchrotron emission. At odds with previous claims, we find no evidence of a diffuse dust component in M87, which is not unexpected in the harsh X-ray environment of this radio galaxy sitting at the core of the Virgo Cluster.Comment: Letter accepted for publication in A&A (Herschel special issue

Activation kinetics of single P2X receptors

After the primary structure of P2X receptors had been identified, their function had to be characterized on the molecular level. Since these ligand-gated ion channels become activated very quickly after binding of ATP, methods with adequate time resolution have to be applied to investigate the early events induced by the agonist. Single-channel recordings were performed to describe conformational changes on P2X2, P2X4, and P2X7 receptors induced by ATP and also by allosteric receptor modifiers. The main results of these studies and the models of P2X receptor kinetics derived from these observations are reviewed here. The investigation of purinoceptors by means of the patch clamp technique following site-directed mutagenesis will probably reveal more details of P2X receptor function at the molecular level