Exp. Eye Res. (1973) 15, 567-575 Relationship of Epithelial Membrane Potentials to Cornea1 Potential* S. D. KLYcEt Department of Physiology and Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut 06510, U.S.A. The rabbit cornea1 potential arises as the sum of three steps across the epithelium. These occur across the squamous cell outer membrane, at the transition region between wing and basal cells, and across the basal cell inner membrane. Variations in cornea1 potential are inversely proportional to outer membrane potential. The latter can be described as the sum of a Goldman-Hodgkin-Katz diffusion potential and a shunt potential. Apparently the central potential step is generated by shunt currents. The potential of the inner mem- brane can be explained on the basis of potassium permeability and distribution. The proposed origin of the outer membrane potential offers an explanation of responses of cornea1 potential to silver ions and agents which elevate tissue levels of cyclic AMP. 1. Introduction Cornea1 potential is generated by the epithelium, but its biophysical basis and rela- tionship to cornea1 transport mechanisms is poorly understood. When rabbit cornea1 potential is neutralized, a fraction of the short-circuit current is borne by the transport of sodium ions to the etroma (Donn, Maurice and Mills, 1959). If the isolated cornea is incubated with agents sustaining adequate tissue levels of cyolic AMP, a larger fraction of the transport current is due to the outward transport of chloride to the tears (Klyce, Neufeld and Zadunaisky, 1973). As with the classic frog skin studies (Ussing and Zerahn, 1951), cornea1 potential has been neutralized in transport studies to simplify the theoretical treatment of ionic fluxes, but it does not follow that the potential so neutralized results from an electrogenic molecular pump mechanism. Hence, the electrophysiology of the boundaries of the epithelium must be examined in deta.il to dissect their serial contributions to the potential measured across the whole structure. Cornea1 potential arises as the sum of potential steps across serial epithelial mem- branes. Por each serial membrane there are at least three possible interdependent components which determine its potential. These are Goldman-Hodgkin-Katz (Goldman, 1943; Hodgkin and Katz, 1949) diffusion potentials arising from con- centration gradients, electrogenic potentials due, at least conceptually, to molecular pump charge separation effects, and shunt potentials from the presence of parallel passive ion pathways. The present paper will review the nature of the steady state electrical profiles in the rabbit cornea1 epithelium and attempt to assess the relative contributions of shunt potentials and diffusion potentials to the electrical profiles. * This investigation was supported by U.S.P.H.S. Grants EY-00382 to Dr J. A. Zadunaisky and CR-1113 to the Department of Physiology of Yale University. t Present address: Division of Ophthalmology, Stanford University Medical Center, Stanford, Cali- fornia 94305; U.S.A. 567