Volume regulation in the bovine lens and cataract. The involvement of chloride channels.
The purpose of this study was to investigate volume regulation in the lens and its involvement in lens opacification (cataract) and the role of chloride channels in these processes. Single, isolated lens fiber cells from the lens were whole cell patch clamped. When exposed to hypotonic solution, and outwardly rectifying whole-cell current was activated. The current increased from 1.0 to 32.6 pA/pF, reversed at the chloride reversal potential (Ec1 = O mV), and was blocked by the chloride channel blockers 5, nitro-2-(3-phenylpropylamino) benzoate (NPPB) and tamoxifen. Replacing all but 5mM of the external chloride with gluconate caused the reversal potential to shift +33 mV, consistent with a CL- current with a gluconate/chloride permeability ratio of 0.26. When the whole lens of the eye was exposed to hypotonic solution, there was an initial increase in anterior-posterior diameter (5-8 min), representing lens swelling of 6.5%. This was followed by a decrease in volume to a new steady state value that lasted for up to 2 h. In the longer term (> or = 2h), the lenses began to swell again. The simultaneous exposure to hypotonic solution and tamoxifen or NPPB caused swelling and prevented this volume regulation. Lenses incubated in hypotonic solution and hypotonic solution containing tamoxifen becane ipaque after a 2-h incubation period. We conclude that the lens is able to volume regulate. It possesses volume-activated Cl- channels, the inhibition of which results in inhibition of volume regulation, lens swelling and opacification. Our data suggest the long-term prophylactic use of tamoxifen may make the patient more susceptible to cataract.
Zhang
J J
JJ
Eye Research Lab, Physiology Unit, School of Molecular & Medical Biosciences, University of Wales, Cardiff CF1 3US, United Kingdom.
Jacob
T J
TJ
D000818:Animals; D002386:Cataract / Q000139:chemically induced*; D002417:Cattle; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007908:Lens, Crystalline / Q000502:physiology*; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D013629:Tamoxifen / Q000494:pharmacology
D018118:Chloride Channels; D004965:Estrogen Antagonists; D009579:Nitrobenzoates; D013629:Tamoxifen; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid