The mechanisms of calcium homeostasis and signalling in the lens

Rhodes, JD and Sanderson, J (2009) The mechanisms of calcium homeostasis and signalling in the lens. Experimental Eye Research, 88 (2). pp. 226-234. ISSN 1096-0007

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    Abstract

    Excessive Ca2+ can be detrimental to cells and raised levels of Ca2+ in human lenses with cortical cataract have been found to play a major role in the opacification process. Ca2+ homeostasis is therefore, recognised as having fundamental importance in lens pathophysiology. Furthermore, Ca2+ plays a central role as a second messenger in cell signalling and mechanisms have evolved which give cells exquisite control over intracellular Ca2+ ([Ca2+]i) via an array of specialised regulatory and signalling proteins. In this review we discuss these mechanisms as they apply to the lens. Ca2+ levels in human aqueous humour are approximately 1 mM and there is a large, 10,000 fold, inwardly directed gradient across the plasma membrane. In the face of such a large gradient highly efficient mechanisms are needed to maintain low [Ca2+]i. The Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+-ATPase (PMCA) actively remove Ca2+ from the cells, whereas the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) sequesters Ca2+ in the endoplasmic reticulum (ER) Ca2+ store. In lens epithelial cells the dominant role is played by the ATPases, whilst in the fibre cells NCX activity appears to be more important. Usually, [Ca2+]i can be increased in a number of ways. Ca2+ influx through the plasma membrane, for example, is mediated by an array of channels with evidence in the lens for the presence of voltage-operated Ca2+ channels (VOCCs), receptor-operated Ca2+ channels (ROCCs) and channels mediating store-operated Ca2+ entry (SOCE). Ca2+ signalling is initiated via activation of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTK) of which the lens expresses a surprisingly diverse array responding to various neurotransmitters, hormones, growth factors, autocoids and proteases. Downstream of plasma membrane receptors are IP3-gated channels (IP3Rs) and ryanodine receptors (RYRs) located in the ER, which when activated cause a rapid increase in [Ca2+]i and these have also been identified in the lens. Through an appreciation of the diversity and complexity of the mechanisms involved in Ca2+ homeostasis in normal lens cells we move closer to an understanding of the mechanisms which mediate pathological Ca2+ overload as occurs in the process of cataract formation.

    Item Type: Article
    Faculty \ School: Faculty of Science > School of Biological Sciences
    Faculty of Science > School of Pharmacy
    University of East Anglia > Faculty of Science > Research Groups > Pharmaceutical Cell Biology
    Related URLs:
    Depositing User: Rachel Smith
    Date Deposited: 17 Mar 2011 13:49
    Last Modified: 25 Jul 2018 04:42
    URI: https://ueaeprints.uea.ac.uk/id/eprint/26539
    DOI: 10.1016/j.exer.2008.10.025

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