Functional integrity of proximal tubule cells. Effects of hypoxia and ischemia.
Effects of warm hypoxia and ischemia on electrophysiologic properties of isolated perfused mouse proximal straight tubules were studied. Oxyrase (5 to 10 microliters/mL) was added to the hypoxic and ischemic solutions to lower the oxygen tension to 5 mm Hg. The ischemic solution also simulated acidosis, K+ and lactate accumulation, and substrate deprivation. Twenty-minute tubular perfusion with the hypoxic and ischemic solutions (lumen and bath) at 37 degrees C did not significantly alter basolateral membrane potential, basolateral K+ transference number, or intracellular Na+ activity from control values of -69 +/- 1 mV (N = 91), 0.71 +/- 0.01 (N = 15), and 15.2 +/- 0.8 mM (N = 12), respectively. However, the hypoxic and ischemic perfusions decreased transepithelial potential by 40% (hypoxia: -1.7 +/- 0.1 to -1.1 +/- 0.1 mV [N = 30; P < 0.001]; ischemia: -1.4 +/- 0.1 to -0.82 +/- 0.05 mV [N = 17; P < 0.001]). A similar extent of reduction in transepithelial resistance was observed (hypoxia: 14.3 +/- 1.0 to 9.2 +/- 1.1 omega.cm2 [N = 7; P < 0.005]; ischemia: 12.6 +/- 1.2 to 8.1 +/- 1.0 omega.cm2 [N = 6; P < 0.03]). In addition, neither apical (R(ap)) nor basolateral (Rbl) cell membrane resistances were significantly altered after the ischemic perfusion (control: R(ap) = 369 +/- 48 omega.cm2; Rbl = 92 +/- 11 omega.cm2 [N = 63]; reperfusion: R(ap) = 454 +/- 88 omega.cm2; Rbl = 101 +/- 16 omega.cm2 [N = 21]). It was concluded that tubular cells are able to maintain their electrogenic ionic transport after short-term exposure to hypoxic or ischemic conditions. However, cell-to-cell junctions are damaged by these insults, which could possibly increase leakage and decrease the efficiency of the active transport.
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Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Hirsch
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Morgunov
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D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology*; D007552:Isotonic Solutions / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D009924:Organ Culture Techniques; D010042:Ouabain / Q000494:pharmacology; D010105:Oxygenases / Q000494:pharmacology; D015424:Reperfusion; D000077331:Ringer's Solution; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000187:drug effects
D007552:Isotonic Solutions; D010042:Ouabain; D000077331:Ringer's Solution; D012964:Sodium; D010105:Oxygenases; C072755:Oxyrase; D000254:Sodium-Potassium-Exchanging ATPase