22 research outputs found

    Expression of the chloride channel CLC-K in human airway epithelial cells

    Get PDF
    Airway submucosal gland function is severely disrupted in cystic fibrosis (CF), as a result of genetic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), an apical membrane Cl– channel. To identify other Cl– channel types that could potentially substitute for lost CFTR function in these cells, we investigated the functional and molecular expression of Cl– channels in Calu-3 cells, a human cell line model of the submucosal gland serous cell. Whole cell patch clamp recording from these cells identified outwardly rectified, pH- and calcium-sensitive Cl– currents that resemble those previously ascribed to ClC-K type chloride channels. Using reverse transcription – polymerase chain reaction, we identified expression of mRNA for ClC-2, ClC-3, ClC-4, ClC-5, ClC-6, ClC-7, ClC-Ka, and ClC-Kb, as well as the common ClC-K channel b subunit barttin. Western blotting confirmed that Calu-3 cells express both ClC-K and barttin protein. Thus, Calu-3 cells express multiple members of the ClC family of Cl– channels that, if also expressed in native submucosal gland serous cells within the CF lung, could perhaps act to partially substitute lost CFTR function. Furthermore, this work represents the first evidence for functional ClC-K chloride channel expression within the lung

    Action in context and context in action: Modelling complexity in multimedia systems development

    No full text
    Whereas multimedia systems development (MSD) is inherently complex, and increasingly so, little is known about how multimedia designers manage or cope with this complexity. In particular, little is known about complexity beyond technical and process levels, and how such complexity impacts design activity. In this paper we construct a model of MSD based on the formulation of the broader concept of context complexity. This concept, which subsumes but also transcends technical and process complexity, is used to explain design strategies and their consequences. We identify four design contexts that explain, and are also explained by, complexity. These contexts map out the 'landscape for action' over which design activity takes place. They shape the design environment and the responses taken to it. We use a grounded theory approach to study what designers actually do (as opposed to theorising what they should do). We argue that a better understanding of context determined and context determining strategies better informs interventions aimed at improving MSD design practice. Our main conclusion is that interventions should be directed to those situations where there is a mismatch between the level of complexity in the design context and the level of complexity in the design strategy taken in response to that context. We call these situations 'breakdown' contexts and examine their causes and consequences in greater detail. Our claimed contribution is to broaden the concept of design breakdowns through a specific understanding of the role and impact of (context) complexity in MSD
    corecore