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PMID: 6100864 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Competitive blocking of epithelial sodium channels by organic cations: the relationship between macroscopic and microscopic inhibition constants.

The Journal of membrane biology ·Vol. 76 ·No. 3 ·1983-00-00 ·Pages 235-51

Li JH, Lindemann B

Abstract

Fluctuation analysis of Na current passing the apical membrane in the skin of Rana ridibunda was used to study the kinetics of Na-channel blocking by several organic cations present in the outer solution together with 60 mM Na. The ratios of the apparent off-rate and on-rate constants (the microscopic inhibition constants) thus obtained for triamterene, triaminopyrimidine (TAP), 5,6-diCl-amiloride, 5H-amiloride and amiloride itself are found to be in the mean about sevenfold smaller than the corresponding inhibition constants obtained from macroscopic dose-response curves. The apparent discrepancy is explicable by competition of the organic blocker with the channel block by Na ions (the self-inhibition effect). The type of interaction between extrinsic blockage and self-inhibition may be purely competitive or mixed. However, in case of mixed inhibition the competitive component must dominate the noncompetitive component by at least seven to one.

MeSH Terms
Amiloride/analogs & derivatives,pharmacology Animals Biological Transport Bufo marinus Epithelium/metabolism In Vitro Techniques Ion Channels/drug effects Kinetics Models, Biological Pyrimidines/pharmacology Rana ridibunda Sodium/metabolism Triamterene/pharmacology
Chemicals
Ion Channels Pyrimidines 2,4,6-triaminopyrimidine 5H-amiloride 5,6-dichloroamiloride Amiloride Sodium Triamterene
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Li J H
Lindemann B
References (34)
34 references, click to expand
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Article Info
Journal
The Journal of membrane biology
Abbr.
J Membr Biol
ISSN
0022-2631
DOI
10.1007/BF01870366
Published
1983-00-00
Pages
235-51
Language
English
Region
United States
NLM ID
0211301
Subset
IM
External Links
PubMed source DOI: 10.1007/BF01870366 View journal details
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