ATP-independent membrane depolarization with ischemia in the oxygen-ventilated isolated rat lung.

Abstract

We hypothesize that lung ischemic injury is related to cessation of flow leading to endothelial cell membrane depolarization and activation of oxidant-generating systems. Cell membrane potential was assessed in isolated, oxygen ventilated, Krebs-Ringer bicarbonate buffer-dextran-perfused rat lungs by lung surface fluorescence after infusion of bis-oxonol or 5,5',6,6'-tetrachloro-1, 1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1), voltage-sensitive dyes. Surface fluorometry showed increased bis-oxonol fluorescence (34.7 +/- 3.3% above baseline) and decreased JC-1 fluorescence (24.5 +/- 4.5% below baseline) with ischemia, compatible with membrane depolarization. Fluorescence change was initiated within 1-2 min of the onset of ischemia and was rapidly reversible with reperfusion. Fluorescence changes varied with perfusion flow rate; maximal increase occurred with the transition from 1.8 ml/min to zero flow. Elevation of static intravascular pressure resulted in only a minor increase of bis-oxonol fluorescence. In situ subpleural fluorescence microscopy showed that endothelial cells are the major site of the increased bis-oxonol fluorescence signal with ischemia. These results indicate that endothelial cell membrane depolarization represents an early event with lung ischemia. Since the adenosine triphosphate content of lung was unchanged with ischemia in the O2-ventilated lungs, we postulate that membrane depolarization results from elimination of shear stress, possibly via inactivation of flow-sensitive K+-channels.

• Authors: A B Al-Mehdi, G Zhao, A B Fisher
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 18 Issue 5 Pg. 653-61 (May 1998) ISSN: 1044-1549 [Print] United States
• PMID: 9569235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Barium Compounds
• Chlorides
• Fluorescent Dyes
• Potassium Channel Blockers
• Potassium Channels
• Thiobarbiturates
• barium chloride
• bis(1,3-diethylthiobarbiturate)trimethineoxonol
• Tetraethylammonium
• Adenosine Triphosphate
• Potassium
• Oxygen

Topics

• Adenosine Triphosphate (physiology)
• Animals
• Barium Compounds (pharmacology)
• Capillaries (chemistry, cytology, physiology)
• Chlorides (pharmacology)
• Endothelium, Vascular (chemistry, cytology, physiology)
• Fluorescent Dyes
• Ischemia (physiopathology)
• Lung (blood supply, drug effects, physiology)
• Male
• Membrane Potentials (physiology)
• Oxygen (pharmacology)
• Potassium (pharmacology)
• Potassium Channel Blockers
• Potassium Channels (agonists, physiology)
• Pulmonary Circulation
• Rats
• Rats, Sprague-Dawley
• Tetraethylammonium (pharmacology)
• Thiobarbiturates