Ischemia induces surface membrane dysfunction: Mechanism of altered Na+-dependent glucose transport

Bruce Molitoris, R. Kinne

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Reversible ischemia reduced renal cortical brush border membrane (BBM) Na+-dependent D-glucose uptake (336 ± 31 vs. 138 ± 30 pmol/mg per 2 s, P <0.01) but had no effect on Na+-independent glucose or Na+-dependent L-alanine uptake. The effect on D-glucose uptake was present after only 15 min of ischemia and was due to a reduction in maximum velocity (1913 ± 251 vs. 999 ± 130 pmol/mg per 2 s; P <0.01). This reduction was not due to more rapid dissipation of the Na+ gradient, altered sidedness of the vesicles, or an alteration in membrane potential. Ischemia did, however, reduce the BBM sphingomyelin-to-phosphatidylcholine (SPH/PC) and cholesterol-to-phospholipid ratios and the number of specific high-affinity Na+-dependent phlorizin binding sites (390 ± 43 vs. 146 ± 24 pmol/mg; P <0.01) without altering the binding dissociation constant (K(d)). 20 mM benzyl alcohol also reduced the number of Na+-dependent phlorizin binding sites (418 ± 65 vs. 117 ± 46; P <0.01) without altering K(d). The reduction in Na+-dependent D-glucose transport correlated with ischemic-induced changes in the BBM SPH/PC and cholesterol-to-phospholipid ratios and membrane fluidity. Taken together these data indicate the cellular site responsible for ischemic-induced reduction in renal cortical transcellular glucose transport is the BBM. We propose the mechanism involves marked alterations in BBM lipids leading to large increases in BBM fluidity which reduces the binding capacity of Na+-dependent glucose carriers. These data indicate that reversible ischemia has profound effects on the surface membrane function of epithelial cells.

Original languageEnglish (US)
Pages (from-to)647-654
Number of pages8
JournalJournal of Clinical Investigation
Volume80
Issue number3
StatePublished - 1987
Externally publishedYes

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Microvilli
Ischemia
Glucose
Membranes
Phlorhizin
Membrane Fluidity
Sphingomyelins
Phosphatidylcholines
Phospholipids
Binding Sites
Cholesterol
Benzyl Alcohol
Kidney
Transcytosis
Membrane Lipids
Alanine
Membrane Potentials
Epithelial Cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ischemia induces surface membrane dysfunction : Mechanism of altered Na+-dependent glucose transport. / Molitoris, Bruce; Kinne, R.

In: Journal of Clinical Investigation, Vol. 80, No. 3, 1987, p. 647-654.

Research output: Contribution to journalArticle

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