The Transient Receptor Potential (TRP) gene was originally identified in Drosophila photoreceptors. Since then, 28 mammalian homologues have been reported and classified into 6 families of TRPC, TRPV, TRPM, TRPML, TRPA and TRPP (Nilius et al., 2007). They are ion channels with permeability to calcium, sodium and, in some cases, magnesium. Their importance in physiology and pathology is being increasingly appreciated. Fibroblast-like synoviocytes – the main cell type of the synovial membrane – play important roles in synovial joint homeostasis. For example, they regulate synovial fluid volume and promote lubrication by secreting hyaluronan and lubricin. However, these cells also actively participate in diseases like rheumatoid arthritis, which has hallmarks including synovial hyperplasia and excessive cartilage degradation by secretion of matrix-degrading enzymes. Because calcium signaling is often associated with such processes, we screened for TRP expression in synoviocytes. Immuno-staining using anti-TRPM3 antibody suggested TRPM3 expression in both rabbit synoviocytes and human synovial tissue sections. We investigated whether there is TRPM3 function in synoviocytes using a TRPM3 activator, sphingosine (Grimm et al., 2005). Sphingosine elicited a biphasic intracellular calcium signal, comprising transient and sustained phases. Sphingosine analogues, dimethylsphingosine and dihydrosphingosine, also elicited calcium responses, consistent with TRPM3 involvement. Calcium-free bath solution significantly reduced the transient sphingosine response, whereas gadolinium, lanthanum, and ruthenium red each abolished both the transient and the sustained phases. These blockers did not affect the ATP response. The sustained response was suppressed but not abolished by a functional anti-TRPM3 blocking antibody, while the transient response was unaffected. We observed TRPM3 expression and sphingosine-induced calcium responses in synoviocytes. The data are consistent with the existence of multiple components to the sphingosine response, with TRPM3 contributing to the sustained phase.
Life Sciences 2007 (2007) Proc Life Sciences, PC227
Poster Communications: Expression and function of TRPM3 calcium channel in synoviocytes
Y. Majeed1, J. Naylor1, C. Ciurtin1, J. Li1, A. English2, P. Emery2, D. J. Beech1
1. Institute of Membrane and Systems Biology, University of Leeds, Leeds, United Kingdom. 2. Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, Leeds, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.