Regional Differences in Store-Operated Ca2+ Entry in the Epithelium of the Intact Human Lens

Rhodes, JD, Russell, SL, Illingworth, CD, Duncan, G and Wormstone, IM (2009) Regional Differences in Store-Operated Ca2+ Entry in the Epithelium of the Intact Human Lens. Investigative Ophthalmology & Visual Science, 50 (9). pp. 4330-4336. ISSN 0146-0404

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    Abstract

    An elevated level of Ca2+ is an important factor in cataract, yet precisely how Ca2+ enters the lens is unknown. Lens epithelial cells contain a range of G-protein–coupled receptors and receptor tyrosine kinases that induce increases in intracellular Ca2+. Receptor-associated Ca2+ influx is, therefore, likely to be an important route for Ca2+ influx to the lens. The authors investigated stimulated and passive Ca2+ influx in in situ human lens epithelium. Ca2+ changes in equatorial (E) and central anterior (CA) epithelial cells were monitored with the use of a Ca2+ indicator (Fluo4) and confocal microscopy. Gene expression was monitored by RT-PCR and immunoblotting. Adenosine triphosphate (ATP) induced Ca2+ responses that were smaller in CA than E. Ca2+ store depletion, using ATP (100 µM) or thapsigargin (1 µM), revealed greater relative store capacity and Ca2+ influx in E. Ca2+ influx was blocked by La3+ (0.5 µM) in both regions. Unstimulated Ca2+ influx was greater in E than CA. Greater expression of Orai1 and STIM1 was detected in E than in CA. Greater Ca2+ store capacity and Ca2+ influx in E compared with CA reflects underlying differences in proliferation and differentiation between the regions. The relatively small resting Ca2+ influx in CA epithelium suggests that store-operated Ca2+ entry (SOCE) is the main route of Ca2+ influx in these cells. Greater resting influx and SOCE in E cells suggests that these are a major route for Ca2+ influx into the lens. Increased expression of Orai1 and STIM1 in E could account for the differences in Ca2+ entry. Receptor activation will modulate Ca2+ influx, and inappropriate activity may contribute to cortical cataract.

    Item Type: Article
    Faculty \ School: Faculty of Science > School of Biological Sciences
    Related URLs:
    Depositing User: Deborah Clemitshaw
    Date Deposited: 07 Mar 2011 14:12
    Last Modified: 25 Jul 2018 04:38
    URI: https://ueaeprints.uea.ac.uk/id/eprint/25699
    DOI: 10.1167/iovs.08-3222

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