Purchase this article with an account.
David Soto, Núria Comes, Elisa Ferrer, Miguel Morales, Artur Escalada, Jordi Palés, Carles Solsona, Arcadi Gual, Xavier Gasull; Modulation of Aqueous Humor Outflow by Ionic Mechanisms Involved in Trabecular Meshwork Cell Volume Regulation. Invest. Ophthalmol. Vis. Sci. 2004;45(10):3650-3661. doi: 10.1167/iovs.04-0060.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. Trabecular meshwork (TM) cell shape, volume, contractility and their interactions with extracellular matrix determine outflow facility. Because cell volume seems essential to TM function, this study was conducted to investigate further the ionic channels and receptors involved in regulatory volume decrease and their roles in modulating outflow facility.
methods. Primary cultures of bovine TM cells were used. K+ and Cl− currents were studied with whole-cell patch clamping. Swelling was induced by hypotonic shock. [Ca2+]i was measured in TM cells loaded with fura-2. Bovine anterior segments were perfused at constant pressure to measure outflow facility.
results. Hypotonic media activated both the high-conductance Ca2+-activated K+ channel (BKCa) and swelling-activated Cl− channel (Clswell) currents and induced release of adenosine 5′-triphosphate (ATP) from TM cells. ATP activated P2Y2 receptors with the following profile: ATP = uridine 5′-triphosphate (UTP) > adenosine 5′-O-(3-thiotriphosphate) (ATP-γ S) > adenosine 5′-diphosphate (ADP) = uridine 5′-diphosphate (UDP), and increased BKCa current. Hypotonic medium initially decreased outflow facility in perfused anterior segments, which recovered with time to baseline levels. Addition of tamoxifen or iberiotoxin (Clswell and BKCa blockers, respectively) lengthened the recovery phase, which implies that these channels participate in cell volume regulation. In contrast, an activator of BKCas (NS1619) produced the opposite effect.
conclusions. Cell swelling activates a regulatory volume decrease mechanism that implies activation of K+ and Cl− currents and participation of P2Y2 receptors. Because previous studies have shown that intracellular volume of TM cells is an important determinant of outflow facility, it seems feasible that cell volume regulation would be part of the homeostatic mechanisms of the TM, to regulate the outflow pathway.
This PDF is available to Subscribers Only