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Twenty years of fluorescence imaging of intracellular chloride.

ABSTRACT: Chloride homeostasis has a pivotal role in controlling neuronal excitability in the adult brain and during development. The intracellular concentration of chloride is regulated by the dynamic equilibrium between passive fluxes through membrane conductances and the active transport mediated by importers and exporters. In cortical neurons, chloride fluxes are coupled to network activity by the opening of the ionotropic GABAA receptors that provides a direct link between the activity of interneurons and chloride fluxes. These molecular mechanisms are not evenly distributed and regulated over the neuron surface and this fact can lead to a compartmentalized control of the intracellular concentration of chloride. The inhibitory drive provided by the activity of the GABAA receptors depends on the direction and strength of the associated currents, which are ultimately dictated by the gradient of chloride, the main charge carrier flowing through the GABAA channel. Thus, the intracellular distribution of chloride determines the local strength of ionotropic inhibition and influences the interaction between converging excitation and inhibition. The importance of chloride regulation is also underlined by its involvement in several brain pathologies, including epilepsy and disorders of the autistic spectra. The full comprehension of the physiological meaning of GABAergic activity on neurons requires the measurement of the spatiotemporal dynamics of chloride fluxes across the membrane. Nowadays, there are several available tools for the task, and both synthetic and genetically encoded indicators have been successfully used for chloride imaging. Here, we will review the available sensors analyzing their properties and outlining desirable future developments.

SUBMITTER: Arosio D

PROVIDER: S-EPMC4148895 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Project description:To determine the growth rate, methodologic clarity, and quality changes in cost-effectiveness analyses (CEAs) and to assess whether the U.S. Panel on Cost-effectiveness in Health and Medicine recommendations affected CEA studies in which imaging technologies were evaluated.Six databases were systematically searched for CEA reports published between 1985 and 2005. All imaging-related studies were selected and grouped according to year, country, and journal of publication, as well as imaging modality and disease being studied. Two readers with formal training in decision analysis and CEA used a seven-point (1, low; 7, high) Likert scale based on reasonableness of assumptions, quality of presentation, and adherence to guidelines to independently evaluate study quality. Quality scores according to year, country, and journal of publication were compared with the unpaired Student t test.The first radiology-related CEA was published in 1985; 111 radiology-related CEAs were published between 1985 and 2005. The average number of studies increased from 1.6 per year between 1985 and 1995 to 9.4 per year between 1996 and 2005. Eighty-six studies were performed to evaluate diagnostic imaging technologies, and 25 were performed to evaluate interventional imaging technologies. Ultrasonography (35.0%), angiography (31.5%), magnetic resonance imaging (22.5%), and computed tomography (19.8%) were evaluated most frequently. Forty-nine studies received government funds; 42 did not disclose the source of funding. The mean quality score was 4.23 +/- 1.12 (standard deviation), without significant improvement over time. Scores in studies performed in the United States were significantly higher than scores in studies that were not performed in the United States (4.45 +/- 1.02 vs 3.61 +/- 1.17, respectively; P < .01). Scores were also higher in journals with three or more CEA articles published during the study period than in journals with two or fewer CEA articles published during this period (4.54 +/- 1.09 vs 3.91 +/- 1.06, respectively; P < .01).CEAs are an important tool with which to analyze the value of diagnostic imaging. However, improvement in the quality of analyses is needed.http://radiology.rsnajnls.org/cgi/content/full/249/3/917/DC1.

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Twenty years of fluorescence imaging of intracellular chloride.

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