EFFECTS OF CA2-CIRCUIT CURRENT - EVIDENCE FOR A CA2+ INHIBITABLE K+ CONDUCTANCE( ON RABBIT TRANSLENS SHORT)

Purpose. To characterize the effects of medium Ca2+ levels on rabbit l ens electrical properties. Early studies with wholly submerged lenses had shown that Ca2+ removal from the bath resulted in an increased Rb efflux, a consequence of an increased Na+ permeability and lens depol arization. Methods. Lenses were bathed within Ussing-type chambers und er short-circuited conditions, an arrangement in which the translens s hort-circuit current (I-SC) is carried across the posterior lens surfa ce mainly by an influx of Na+, and across the anterior face largely by a K+ efflux. Results. Under the present conditions in which the effec ts of Ca2+ were characterized unilaterally, the above established effe cts could only be ascribed to the posterior surface. When Ca2+ removal was limited to the anterior face, the I-SC increased from 11.87+/-1.1 7 to 17.04+/-1.52 mu A/cm(2) (means+/-SE's, n=18; an accompanying tran slens resistance (R(t)) decrease of 0.23+/-0.049 K Omega.cm(2) was als o recorded). Conversely, increasing the control, anterior-bath [Ca2+] from 1.8 to 3.6 mM reduced the K+ efflux-dependent I-sc from 10.54+/-1 .09 to 8.93+/-1.02 (n=10, with an R(t) increase of 0.11+/-0.013). Thes e changes were reversible, Na+-independent, and fully inhibited by the presence of K+ channel blockers (quinidine or Ba2+). Inhibitions of t he Ca2+ effects were also obtained with strontium, a Ca2+ surrogate. T he I-SC was less responsive to changes in the Ca2+ content of the post erior bath. Removal of the cation caused a gradual 1.65+/-0.72 mu A/cm (2) increase (n=9, with an R(t) decrease of 0.090+/-0.021 K Omega.cm(2 )). In the absence of posterior Na+, Ca2+ withdrawal resulted in highl y variable responses, with some specimens exhibiting salient current i ncreases, suggesting that an outwardly directed, posterior efflux of a n anion could also have been affected. During the course of this study it was consistently observed that the removal of Na+ from the anterio r bath led to an I-SC decrease of 2.62+/-0.22 mu A/cm(2) (n=32, with a n R(t) increase of 0.35+/-0.029 K Omega.cm(2)). This change occurred i n both the presence of ouabain and the absence of Ca2+, suggesting tha t it did not result from an inhibition of the Na+-K+ pump current nor from a reversal in putative Na+/Ca2+ exchange activity. Small I-SC inc reases upon anterior Na+ withdrawal (1.68+/-0.17, n=7), consistent wit h Na+ efflux from the lens, could only be observed with KC channels in hibited with Ba2+. Also congruent with the observations of a relativel y limited anterior Na+ permeability, was the finding that the inductio n of nonspecific cation channels with amphotericin B reduced the I-SC by allowing Na+ from the anterior bath to enter the lens. Thus, change s in lens I-SC can differentiate changes in K+ permeability across the native anterior epithelium from changes in Na+ permeability. Conclusi ons. Overall, these results suggest that lens Ca2+-mobilizing agents ( e.g. acetylcholine) could trigger the inhibition of epithelial K+ cond uctance(s) by the direct action of Ca2+ on K+ channels.