title: Functional integrity of proximal tubule cells. Effects of hypoxia and ischemia.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: You
authors.forename: D J
authors.initials: DJ
authors.lastname: Hirsch
authors.forename: N S
authors.initials: NS
authors.lastname: Morgunov
mesh_terms: 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
chemical_list: D007552:Isotonic Solutions; D010042:Ouabain; D000077331:Ringer's Solution; D012964:Sodium; D010105:Oxygenases; C072755:Oxyrase; D000254:Sodium-Potassium-Exchanging ATPase