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The pump and leak steady-state concept with a variety of regulated leak pathways.
J Membr Biol 2001; 184(3):321-30JM

Abstract

The paper will reflect on how Ussing has affected my own scientific work and how he created much of the framework within which I have been working. I have used five examples: (i) The first description of a 1:1 exchange diffusion was introduced by Ussing in 1947 and has been found to be of great physiological significance in most cells. We found that Cl- transport in Ehrlich ascites tumor cells (EATC) was completely dominated by an exchange diffusion process, as defined by Ussing, and, thus, the Cl- conductance was much lower than previously estimated from measurements of unidirectional tracer fluxes. This had a major influence on my later description of a swelling-activated Cl- conductance. (ii) The pump-leak steady-state concept for cell volume control was introduced by Krogh in 1946, but it was developed in detail by Leaf and Ussing in 1959. This concept was the basis for me and others, when we later found that the passive ion leaks play an active role in cell volume control. (iii) The use of isotopes and Ussing's famous flux ratio equation provided an ingenious instrument for distinguishing the various transport routes. We used this to identify the Na,K,2Cl cotransport system as accounting for maintaining a [Cl-]i in the EATC far above thermodynamic equilibrium, as well as accounting for the ion uptake during a regulatory volume increase (RVI) in EATC, similar to what Ussing had found in frog skin. (iv) Short-circuit current setup in the Ussing chamber is still used in laboratories around the world to study ion transport across epithelia. A few results on Cl- transport across the operculum epithelium of the small eurohaline fish Fundulus heteroclitus mounted in small Ussing chambers are presented. (v) Shrinkage-activated Na+ conductance and its possible role in isotonic secretion in frog skin glands is finally discussed.

Authors+Show Affiliations

August Krogh Institute, University of Copenhagen, 13, Universitetsparken, 2100 Copenhagen 0, Denmark.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11891558

Citation

Hoffmann, E K.. "The Pump and Leak Steady-state Concept With a Variety of Regulated Leak Pathways." The Journal of Membrane Biology, vol. 184, no. 3, 2001, pp. 321-30.
Hoffmann EK. The pump and leak steady-state concept with a variety of regulated leak pathways. J Membr Biol. 2001;184(3):321-30.
Hoffmann, E. K. (2001). The pump and leak steady-state concept with a variety of regulated leak pathways. The Journal of Membrane Biology, 184(3), pp. 321-30.
Hoffmann EK. The Pump and Leak Steady-state Concept With a Variety of Regulated Leak Pathways. J Membr Biol. 2001 Dec 1;184(3):321-30. PubMed PMID: 11891558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The pump and leak steady-state concept with a variety of regulated leak pathways. A1 - Hoffmann,E K, Y1 - 2002/02/05/ PY - 2001/08/15/received PY - 2002/3/14/pubmed PY - 2002/8/21/medline PY - 2002/3/14/entrez SP - 321 EP - 30 JF - The Journal of membrane biology JO - J. Membr. Biol. VL - 184 IS - 3 N2 - The paper will reflect on how Ussing has affected my own scientific work and how he created much of the framework within which I have been working. I have used five examples: (i) The first description of a 1:1 exchange diffusion was introduced by Ussing in 1947 and has been found to be of great physiological significance in most cells. We found that Cl- transport in Ehrlich ascites tumor cells (EATC) was completely dominated by an exchange diffusion process, as defined by Ussing, and, thus, the Cl- conductance was much lower than previously estimated from measurements of unidirectional tracer fluxes. This had a major influence on my later description of a swelling-activated Cl- conductance. (ii) The pump-leak steady-state concept for cell volume control was introduced by Krogh in 1946, but it was developed in detail by Leaf and Ussing in 1959. This concept was the basis for me and others, when we later found that the passive ion leaks play an active role in cell volume control. (iii) The use of isotopes and Ussing's famous flux ratio equation provided an ingenious instrument for distinguishing the various transport routes. We used this to identify the Na,K,2Cl cotransport system as accounting for maintaining a [Cl-]i in the EATC far above thermodynamic equilibrium, as well as accounting for the ion uptake during a regulatory volume increase (RVI) in EATC, similar to what Ussing had found in frog skin. (iv) Short-circuit current setup in the Ussing chamber is still used in laboratories around the world to study ion transport across epithelia. A few results on Cl- transport across the operculum epithelium of the small eurohaline fish Fundulus heteroclitus mounted in small Ussing chambers are presented. (v) Shrinkage-activated Na+ conductance and its possible role in isotonic secretion in frog skin glands is finally discussed. SN - 0022-2631 UR - https://www.unboundmedicine.com/medline/citation/11891558/The_pump_and_leak_steady_state_concept_with_a_variety_of_regulated_leak_pathways_ L2 - https://dx.doi.org/10.1007/s00232-001-0102-5 DB - PRIME DP - Unbound Medicine ER -