Jon Sinclair
University of Gothenburg
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Featured researches published by Jon Sinclair.
Neurochemistry International | 2000
Elisabeth Hansson; Håkan Muyderman; Julia Leonova; Louise Allansson; Jon Sinclair; Fredrik Blomstrand; Thorleif Thorlin; Michael Nilsson; Lars Rönnbäck
Astroglia have the capacity to monitor extracellular glutamate (Glu) and maintain it at low levels, metabolize Glu, or release it back into the extracellular space. Glu can induce an increase in astroglial cell volume with a resulting decrease of the extracellular space, and thereby alter the concentration of extracellular substances. Many lines of evidence show that K(+) can be buffered within the astroglial gap-junction-coupled network, and recent results show that gap junctions are permeable for Glu. All these events occur dynamically: the astroglial network has the capacity to interfere actively with neurotransmission, thereby contributing to a high signal-to-noise ratio for the Glu transmission. High-quality neuronal messages during normal physiology can then be maintained. With the same mechanisms, astroglia might exert a neuroprotective function in situations of moderately increased extracellular Glu concentrations, i.e., corresponding to conditions of pathological hyper-excitability, or corresponding to early stages of an acute brain injury. If the astroglial functions are failing, neuronal dysfunction can be reinforced.
Neurochemistry International | 2001
Håkan Muyderman; Jon Sinclair; Kent E. Jardemark; Elisabeth Hansson; Michael Nilsson
In the present study, effects of the alpha(2)- and beta-adrenoceptor agonists clonidine and isoproterenol on astrocytes in astroglial/neuronal cocultures from rat cerebral cortex were evaluated. The calcium- and potassium-sensitive dyes fura-2 and potassium-binding benzofuran isophtalate (PBFI) were used to study alterations in intracellular concentrations of calcium ([Ca(2+)](i)) and potassium ([K(+)](i)), respectively, while the perforated patch clamp technique was used to analyze transmembrane currents. Exposure to isoproterenol or clonidine elicited an immediate increase in [Ca(2+)](i) that was totally abolished in calcium-free extracellular media. Isoproterenol also decreased [K(+)](i), but clonidine did not. The reduction in [K(+)](i) was inhibited in Ca(2+)-free media. As evaluated with the perforated patch technique, isoproterenol (10(-6)-10(-4) M) induced a slowly developing and long lasting outward current that also was totally abolished in calcium-free buffer. This current was blocked by external tetraethylammonium (TEA, 10 mM) and charybdotoxin (ChTX, 10 nM), but was not affected by apamin (50 nM). The current-to-voltage (I-V) relationships for the isoproterenol-induced currents showed a markedly negative reversal potential, -96 mV+/-7, (mean+/-S.D., n=5). These results suggest that the stimulation of astroglial beta-adrenoceptors by isoproterenol opens calcium-activated potassium channels (K((Ca))). Preincubation with forskolin significantly increased the isoproterenol-induced currents compared with controls, indicating that the opening of astroglial K((Ca)) channels after beta-adrenergic stimulation not only depends on [Ca(2+)](i) but also synergistically involves the cAMP transduction system to which beta-adrenoceptors are known to be positively coupled.
PLOS ONE | 2016
Monica Llano-Diez; Jon Sinclair; Takashi Yamada; Mei Zong; Jérémy Fauconnier; Shi-Jin Zhang; Abram Katz; Kent Jardemark; Håkan Westerblad; Daniel C. Andersson; Johanna T. Lanner
The metabolic syndrome is associated with prolonged stress and hyperactivity of the sympathetic nervous system and afflicted subjects are prone to develop cardiovascular disease. Under normal conditions, the cardiomyocyte response to acute β-adrenergic stimulation partly depends on increased production of reactive oxygen species (ROS). Here we investigated the interplay between beta-adrenergic signaling, ROS and cardiac contractility using freshly isolated cardiomyocytes and whole hearts from two mouse models with the metabolic syndrome (high-fat diet and ob/ob mice). We hypothesized that cardiomyocytes of mice with the metabolic syndrome would experience excessive ROS levels that trigger cellular dysfunctions. Fluorescent dyes and confocal microscopy were used to assess mitochondrial ROS production, cellular Ca2+ handling and contractile function in freshly isolated adult cardiomyocytes. Immunofluorescence, western blot and enzyme assay were used to study protein biochemistry. Unexpectedly, our results point towards decreased cardiac ROS signaling in a stable, chronic phase of the metabolic syndrome because: β-adrenergic-induced increases in the amplitude of intracellular Ca2+ signals were insensitive to antioxidant treatment; mitochondrial ROS production showed decreased basal rate and smaller response to β-adrenergic stimulation. Moreover, control hearts and hearts with the metabolic syndrome showed similar basal levels of ROS-mediated protein modification, but only control hearts showed increases after β-adrenergic stimulation. In conclusion, in contrast to the situation in control hearts, the cardiomyocyte response to acute β-adrenergic stimulation does not involve increased mitochondrial ROS production in a stable, chronic phase of the metabolic syndrome. This can be seen as a beneficial adaptation to prevent excessive ROS levels.
Analytical Chemistry | 2005
Johan Pihl; Jon Sinclair; Eskil Sahlin; Mattias Karlsson; Fredrik Petterson; Jessica Olofsson; Owe Orwar
Archive | 2003
Owe Orwar; Daniel Chiu; Johan Pihl; Jon Sinclair; Jessica Olofsson; Matthias Karlsson; Kent Jardemark
Analytical Chemistry | 2002
Jon Sinclair; Johan Pihl; Jessica Olofsson; Mattias Karlsson; Kent Jardemark; Daniel T. Chiu; Owe Orwar
Journal of the American Chemical Society | 2003
Max Davidson; Mattias Karlsson; Jon Sinclair; Kristin Sott; Owe Orwar
Proceedings of the National Academy of Sciences of the United States of America | 2005
Jessica Olofsson; Helen Bridle; Jon Sinclair; Daniel Granfeldt; Eskil Sahlin; Owe Orwar
Analytical Chemistry | 2004
Jessica Olofsson; Johan Pihl; Jon Sinclair; Eskil Sahlin; Mattias Karlsson; Owe Orwar
Archive | 2003
Mattias Karlsson; Owe Orwar; Daniel T. Chiu; Jon Sinclair; Kent Jardemark; Jessica Olofsson; Johan Pihl; Cecilia Farre