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) All Versions of this Article: 290/5/C1355    most recent 00501.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal 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 ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Chen, P. Articles by McDonough, A. A. Search for Related Content PubMed PubMed Citation Articles by Chen, P. Articles by McDonough, A. A.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Modest dietary K⁺ restriction provokes insulin resistance of cellular K⁺ uptake and phosphorylation of renal outer medulla K⁺ channel without fall in plasma K⁺ concentration

¹Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California; and ²Department of Pharmacology, New York Medical College, Valhalla, New York

Submitted 7 October 2005 ; accepted in final form 5 December 2005

Extracellular K⁺ concentration ([K⁺]) is closely regulated by the concerted regulatory responses of kidney and muscle. In this study, we aimed to define the responses activated when dietary K⁺ was moderately reduced from a control diet (1.0% K⁺) to a 0.33% K⁺ diet for 15 days. Although body weight and baseline plasma [K⁺] (4.0 mM) were not reduced in the 0.33% K⁺ group, regulatory responses to conserve plasma [K⁺] were evident in both muscle and kidney. Insulin-stimulated clearance of K⁺ from the plasma was estimated in vivo in conscious rats with the use of tail venous and arterial cannulas. During infusion of insulin·(50 mU·kg^–1·min^–1), plasma [K⁺] level fell to 3.2 ± 0.1 mM in the 1.0% K⁺ diet group and to only 3.47 ± 0.07 mM in the 0.33% K⁺ diet group (P < 0.01) with no reduction in urinary K⁺ excretion, which is evidence of insulin resistance to cellular K⁺ uptake. Insulin-stimulated cellular K⁺ uptake was quantitated by measuring the K⁺ infusion rate necessary to clamp plasma K⁺ at baseline (in µmol·kg^–1·min^–1) during 5 mU of insulin·kg^–1·min^–1 infusion: 9.7 ± 1.5 in 1% K⁺ diet was blunted to 5.2 ± 1.7 in the 0.33% K⁺ diet group (P < 0.001). Muscle [K⁺] and Na⁺-K⁺-ATPase activity and abundance were unchanged during the 0.33% K⁺ diet. Renal excretion, which was measured overnight in metabolic cages, was reduced by 80%, from 117.6 ± 10.5 µmol/h/animal (1% K⁺ diet) to 24.2 ± 1.7 µmol/h/animal (0.33% K⁺ diet) (P < 0.001). There was no significant change in total abundance of key renal K⁺ transporters, but 50% increases in both renal PTK cSrc abundance and ROMK phosphorylation in the 0.33% K⁺ vs. 1% K⁺ diet group, previously established to be associated with internalization of ROMK. These results indicate that plasma [K⁺] can be maintained during modest K⁺ restriction due to a decrease in insulin-stimulated cellular K⁺ uptake as well as renal K⁺ conservation mediated by inactivation of ROMK, both without a detectable change in plasma [K⁺]. The error signals inciting and maintaining these responses remain to be identified.

potassium homeostasis; Na⁺-K⁺-ATPase; H⁺-K⁺-ATPase; protein tyrosine kinase; cSrc

This article has been cited by other articles:

				D. Zheng, A. Perianayagam, D. H. Lee, M. D. Brannan, L. E. Yang, D. Tellalian, P. Chen, K. Lemieux, A. Marette, J. H. Youn, et al. AMPK activation with AICAR provokes an acute fall in plasma [K+] Am J Physiol Cell Physiol, January 1, 2008; 294(1): C126 - C135. [Abstract] [Full Text] [PDF]