Cl secretagogues reduce basolateral K permeability in the rabbit corneal epithelium

The stromal-to-tear transport of Cl by the rabbit corneal epithelium is increased by pharmacological effectors (secretagogues) that raise cAMP. It is well established that such secretagogues increase the apical membrane permeability to Cl and thus facilitate the efflux of the anion. However, we and others have found that cAMP-elevating agents frequently decrease the transepithelial potential difference across the rabbit cornea. The mechanism underlying this latter phenomenon had not been characterized. In this report, transepithelial and microelectrode studies were combined with measurements of unidirectional fluxes of Cl-36, Na-22 and Rb-86 to show that secretagogues known to act via cAMP also decrease the K permeability of the basolateral membrane, which by cellular depolarization would decrease apical Cl secretion. This effect was increasingly pronounced as a function of concentration when agents (e.g., epinephrine, isoproterenol) were applied to the apical side of the preparations. The addition of these agonists to the basolateral bathing solution, or of forskolin to the apical side, solely elicited inhibitions of basolateral K permeability. It seems that apical Cl and basolateral K conductances are independently and inversely regulated by cAMP. The opposite effects that cAMP could have on fluid secretion and epithelial thickness, by increasing apical Cl permeability but decreasing basolateral K permeability, may serve as a mechanism to maintain epithelial thickness within a narrow range.