Regulatory volume increase of human non-pigmented ciliary epithelial cells.
Cells (ODM/SV40) derived from human non-pigmented ciliary epithelial cells were studied by electronic cell sizing. After transiently suspending the cells in hypotonic solution, isotonicity was restored by addition of sucrose. The cell volumes (vc) initially fell below those of control isotonic suspensions, and subsequently increased towards the baseline level. This secondary increase in vc is termed the regulatory volume increase (RVI). Results obtained with ionic substitutions and transport inhibitors indicate that four ionic mechanisms can support the RVI in these cells: coupled Na+/H+ and Cl-/HCO3- antiports, a Na+/Cl- symport, a Na+/K+/2Cl- symport, and a Na+ channel in parallel with a Cl-/HCO3- antiport. Arachidonic acid metabolites regulate the RVI very differently from their effects on the regulatory volume response (RVD) of the same cells to cell swelling. Prostaglandin E2 (PGE2), leukotriene (LTD4) and the PKC-inhibitor staurosporine all inhibit the RVI. Blockade of the cyclooxygenase, lipoxygenase and epoxygenase pathways of arachidonic acid metabolism [with 5,8,11,14-eicosatetraynoic acid (ETYA)] produces a net acceleration of the RVI. In contrast, PGE2 and staurosporine stimulate, LTD4 has no effect, and ETYA inhibits the RVD. We suggest that knowledge of the ionic mechanisms and intracellular signalling underlying the RVI phenomenon may provide a basis for reducing the rate of net aqueous humor formation by increasing the rate of reabsorption of fluid from the aqueous humor into the non-pigmented ciliary epithelial cells.
Civan
M M
MM
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6085, USA.
Coca-Prados
M
M
Peterson-Yantorno
K
K
D001693:Biological Transport, Active / Q000502:physiology; D048429:Cell Size / Q000502:physiology*; D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology / Q000502:physiology*; D015777:Eicosanoids / Q000502:physiology; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D010770:Phosphotransferases / Q000502:physiology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology
D015777:Eicosanoids; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D000254:Sodium-Potassium-Exchanging ATPase