Ion transport mechanisms in native rabbit nasal airway epithelium.
Net ion transports in rabbit nasal airway epithelium (RNAE) were estimated from unidirectional fluxes of 22Na+, 36Cl-, and 86Rb+ (K+ tracer), short-circuit current (Isc), and epithelial conductance (Gt) under short-circuit conditions in excised parallel RNAE from the two sides of the nasal septum mounted in Ussing chambers at 37 degrees C. Net Na+ absorption (JNa; 76 nmol.min-1.cm-2) was nearly equal to the net charge flux (Jnet), equivalent to the control Isc of 137 microA/cm2 (Jnet = Isc/zF = 85 neq.min-1.cm-2). Secretions of Cl- (9 nmol.min-1.cm-2) and K+ (Rb+) (1.2 nmol.min-1.cm-2) were small. Intra-animal variations between right- and left-side Isc values were small compared with large interanimal variations, suggesting long-term regulation of JNa. Serosal ouabain (10(-4) M) abolished Isc. Mucosal amiloride (10(-4) M) maximally inhibited Isc by 68% and JNa by 78%, abolished K+ (Rb+) secretion, increased Cl- secretion slightly (to 16 nmol.min-1.cm-2), and decreased control Gt (13.4 mS/cm2) by 26%. Amiloride-insensitive JNa was inhibited approximately 50% by mucosal hydrochlorothiazide (10(-4) M) but not by mucosal bumetanide, phloridzine, or ethoxzolamide. The Cl- secretion was abolished by serosal bumetanide (10(-4) M) and also by mucosal diphenylamine-2-carboxylate (2.5.10(-4) M) or bumetanide (10(-4) M). Serosal Ba2+ (2 mM) inhibited JNa and increased K+ (Rb+) secretion. The latter was blocked by mucosal Ba2+. Passive Cl- (but not Na+) fluxes varied proportionally with Gt and were approximately four times higher than passive Na+ fluxes, suggesting 1) significant anion selectivity of a low-resistance paracellular pathway and 2) separate routes for paracellular Cl- and Na+ fluxes. We conclude that RNAE is a suitable model organ for studies of regulation of JNa in native human airway epithelia.
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
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Röpke
S
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Carstens
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M
Holm
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O
Frederiksen
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001692:Biological Transport; D002034:Bumetanide / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000502:physiology; D004594:Electrophysiology; D004848:Epithelium / Q000378:metabolism; D006852:Hydrochlorothiazide / Q000494:pharmacology; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D026902:Potassium Channel Blockers; D011817:Rabbits; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects; D014882:Water-Electrolyte Balance; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D026902:Potassium Channel Blockers; D015222:Sodium Channels; D062367:ortho-Aminobenzoates; D006852:Hydrochlorothiazide; D002034:Bumetanide; D001464:Barium; D000584:Amiloride; C001209:fenamic acid; D012964:Sodium