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Pasantes Morales, H; Ochoa-de la Paz, LD; Lezama, R; Toscano, B (2005)


PFLUG ARCH EUR J PHY 449(6):526-536
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An increase in extracellular KCl ([ KCl](o)) occurs under various pathological conditions in the retina, leading to retinal swelling and possible neuronal damage. The mechanisms of this KClo-induced retinal swelling were investigated in the present study, with emphasis on the Cl- transport mechanisms. Increasing [KCl](o) ( from 5 to 70 mM) led to concentration- dependent swelling in chicken retinas. The curve relating the degree of swelling to [KCl](o) was biphasic, with one component from 5 to 35 mM [ KCl] o and another from 35 to 100 mM. As Cl- omission prevented swelling in all conditions, the effect of cotransporter or Cl- channel blockers was examined to investigate the mechanisms of Cl- influx. The cotransporter blockers bumetanide and DIOA reduced swelling by 68% and 76%, respectively at [KCl](o) 25 mM (K25), and by 14 - 17% at [ KCl](o) 54 mM (K54). The Cl- channel blockers NPPB and niflumic acid did not a. ect swelling at K25 but reduced it by 90 - 95% at K54 ( NPPB IC50 60.7 muM). Furosemide showed an atypical e. ect, decreasing swelling by 14% at K25 and by 95% at K54 ( IC50 173.9 muM). Na+ omission decreased swelling at K25 but not at K54. These results suggest the contribution of cotransporters to Cl- influx at K25 and of Cl- channels at K54. At K25, swelling was found in the ganglion cell layer and in the lower half of the inner nuclear layer. With K54, swelling occurred in all inner retinal layers. The ganglion cell layer swelling was due to both Muller cell end-foot and ganglion cell soma swelling. K54 also induced ganglion cell damage as shown by disorganized, pyknotic and refringent nuclei.