HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Levin, M. H. Articles by Verkman, A. S. Search for Related Content PubMed PubMed Citation Articles by Levin, M. H. Articles by Verkman, A. S.

Potential Difference Measurements of Ocular Surface Na⁺ Absorption Analyzed Using an Electrokinetic Model

¹From the Departments of Medicine and Physiology and the Cardiovascular Research Institute, and the ²Graduate Group in Biophysics, University of California, San Francisco, California.

PURPOSE. Corneal and conjunctival epithelia are capable of transcellular Na⁺ absorption and Cl^– secretion, which drives water movement across these tissues. A recent study demonstrated with a new open-circuit potential difference (PD) technique that Cl^– moves across the ocular surface in mice through Ca²⁺- and cAMP-sensitive Cl^– channels, the latter pathway being the cystic fibrosis (CF) transmembrane conductance regulator (CFTR). The purpose of the present study was to identify transporting mechanisms involved in Na⁺ absorption and to develop a mathematical model of ocular surface ion transport to quantify the relative magnitudes of and electrochemical coupling among transporting processes.

METHODS. PDs across the fluid-bathed ocular surface were measured in anesthetized wild-type and CF mice in response to Na⁺, Cl^–, and K⁺ ion substitution and transporter agonists, inhibitors, and substrates. An electrokinetic model of the ocular surface epithelium was developed to simulate PD measurements, which involved computation of membrane potentials and cell [Na⁺], [K⁺], [Cl^–] and volume from transporter activities and extracellular ion concentrations.

RESULTS. Na⁺ replacement produced a 6 ± 2-mV depolarization that was blocked by amiloride (K_i 0.8 µM) and benzamil (K_i 0.2 µM). The Na⁺-dependent depolarization by amiloride was significantly greater in CF mice (19 ± 3 mV). In wild-type mice, D-, but not L-glucose produced a phloridzin-sensitive, 4.1-mV hyperpolarization in the presence of Na⁺ and amiloride, with a K_m for D-glucose of 2.5 mM. Glycine and L-arginine also produced Na⁺-dependent hyperpolarizations. The epithelial transport model accurately reproduced experimental PD measurements.

CONCLUSIONS. PD measurements coupled with model computations defined quantitatively the roles of Na⁺ and Cl^– transport processes in ocular surface ion and fluid secretion, and indicated that CFTR-dependent changes in apparent epithelial Na⁺ channel (ENaC) activity could be accounted for by electrochemical coupling, without requiring ENaC-CFTR interactions. The data and modeling also predicted significant enhancement of ocular surface fluid secretion by ENaC inhibitors and CFTR activators as possible therapies for dry eye syndromes.

This article has been cited by other articles:

				W. Namkung, Y. Song, A. D. Mills, P. Padmawar, W. E. Finkbeiner, and A. S. Verkman In Situ Measurement of Airway Surface Liquid [K+] Using a Ratioable K+-sensitive Fluorescent Dye J. Biol. Chem., June 5, 2009; 284(23): 15916 - 15926. [Abstract] [Full Text] [PDF]