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Elena Abad, Gisela Lorente, Núria Gavara, Miguel Morales, Arcadi Gual, Xavier Gasull; Activation of Store-Operated Ca2+ Channels in Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(2):677-686. doi: https://doi.org/10.1167/iovs.07-1080.
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purpose. In nonexcitable cells, Gq-coupled membrane receptor activation induces a biphasic increase in intracellular calcium ([Ca2+]i) expressed as an initial IP3-dependent release from intracellular stores followed by a sustained Ca2+ influx from the extracellular space that involves store-operated Ca2+ channels (SOCs). In trabecular meshwork (TM) cells, contractile agonists such as bradykinin (BK) and endothelin-1 (ET-1) induce this type of Ca2+ signaling. Given that trabecular outflow is modified by tissue contractility, the authors characterized SOCs and studied their participation in TM cell contractility.
methods. [Ca2+]i was measured in cultured bovine TM cells loaded with Fura-2. Ca2+ currents were recorded using the patch clamp technique. Cell contractility measurements were assessed by traction microscopy.
results. BK and ET-1 activate a store-operated Ca2+ entry that was greatly reduced in the absence of extracellular Ca2+ or by preincubation with SOC blocker 2-APB or SKF96365. Store-operated Ca2+ currents were also activated by intracellular dialysis with IP3 + EGTA or after stimulation with thapsigargin. Electrophysiological characterization supports the presence of Ca2+ release-activated Ca2+ channels (CRACs) and nonselective cation channels, of which TRPC1 and TRPC4 channels may be candidate TRPs detected in TM cells. Extracellular Ca2+ entry through SOCs is not required for TM cell contraction in response to BK or ET-1, but it modulates this process.
conclusions. Extracellular Ca2+ entry in TM cells in response to agonist stimulation and store-depletion is mediated by the activation of SOCs, which do not contribute to cell contraction but which may activate regulatory mechanisms to prevent excessive contraction. CRAC and TRPC channels involved represent interesting modulators of TM function to improve aqueous humor outflow.
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