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General Physiology and Biophysics Vol.35, No.3, p.259–271, 2016 |
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Title: Effects of Cd2+ on the epithelial Na+ channel (ENaC) investigated by experimental and modeling studies | ||
Author: Maria Mernea, Roxana Ulă reanu, Octavian Călborean, Sergiu Chira, Octavian Popescu, Dan F. Mihailescu, Dana Cucu | ||
Abstract: The function of the epithelial Na+ channel from the apical membrane of many Na+ transporting epithelia is modulated by various chemical compounds from the extracellular space, such as heavy metals, protons or chloride ions. We have studied the effect of extracellular Cd2+ on the function of the epithelial Na+ channel (ENaC) in heterologously expressed Xenopus laevis oocytes and Na+-transporting epithelia. We assayed channel function as the amiloride-sensitive sodium current (INa). Cd2+ rapidly and voltage-independently inhibited INa in oocytes expressing αβγ Xenopus ENaC (xENaC). The extracellular Cd2+ inhibited Na+ transport and showed no influence on ENaC trafficking, as revealed by concomitant measurements of the transepithelial current, conductance and capacitance in Na+-transporting epithelia. Instead, amiloride inhibition was noticeably diminished in the presence of Cd2+ on the apical membrane. Using molecular modeling approaches, we describe the amiloride binding sites in rat and xENaC structures, and we present four putative binding sites for Cd2+. These results indicate that ENaC functions as a sensor for external Cd2+. |
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Keywords: ENaC — Xenopus laevis — Cd2+ — A6 epithelia | ||
Published online: 13-Jun-2016 | ||
Year: 2016, Volume: 35, Issue: 3 | Page From: 259, Page To: 271 | |
doi:10.4149/gpb_2015054 |
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