Bioelectric properties and ion transport of excised rabbit trachea

Abstract

Bioelectric properties and 22Na+ and 36Cl- isotopic flows across rabbit trachea, an airway epithelium without submucosal glands, were measured in vitro. One hundred twenty-two excised tracheas exhibited a mean transepithelial electric potential difference (PD) of 12 mV (lumen negative), a conductance (G) of 8.5 mS X cm-2, and a short-circuit current (Isc) of 90 microA X cm-2. G remained stable for more than 3 h, but Isc and PD fell slowly (10%/h). G was inversely correlated with PD, but Isc and G were not correlated. Na+ was absorbed under both open-circuit (1.7 mueq. cm-2 X h-1) and short-circuit (2.2 mueq X cm-2 X h-1) conditions. Net Na+ transport accounted for 70% of Isc of the short-circuited trachea. Net Cl- flow in the absorptive direction approximated that of Na+ under open-circuit conditions (1.6 mueq X cm-2 X h-1). Under short-circuit conditions the small net flow of Cl- in the direction of secretion (0.4 mueq X cm-2 X h-1) was not significant. Both unidirectional Cl- fluxes were correlated with G; [14C]-mannitol permeability and Na+ flows were weakly or not correlated with G. We found no evidence of net HCO-3 or proton transport. Acetylcholine (10(-4) M), phenylephrine (10(-5) M), or isoproterenol (10(-5) M) induced no change in bioelectric properties or ion flows. We conclude that the rabbit trachea is primarily a Na+ absorbing epithelium. The absence of a correlation between mannitol permeability and G suggests that much of the Cl- conductance is transcellular. Whereas insensitivity of rabbit trachea to cholinergic and alpha-adrenergic agents is compatible with the absence of glands, the lack of response to beta-adrenergic agonists denotes a species difference (compared with canine trachea) in airway-surface epithelial cell function.

Signature current of SO2-induced bronchitis in rabbit.

“…Neither the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 10 Ϫ3 M, n ϭ 3), a membrane-permeable cAMP analogue 8-(4-chlorophenylthio)-adenosine 3Ј:5Ј-cyclic monophosphate (cpt-cAMP, 10 Ϫ4 M, n ϭ 2), nor a stimulant of adenylyl cyclase forskolin (10 Ϫ5 M, n ϭ 3) induced any significant responses in normal tissues. This electric refractoriness of rabbit tracheas to ␤-adrenergic agonists or forskolin has been documented (13,14,19,22). Surprisingly, however, in SO 2 -bronchitis rabbit trachea, both ISO (n ϭ 5) and ADO (n ϭ 4) caused a significant increase in Isc associated with increased electric conductance (Fig.…”

“…An additional possibility is an interference of the passive cellular Cl Ϫ pathway due to the thickened epithelial layer produced through SO 2 exposure. A low in vitro PD observed in normal rabbit trachea has been explained by the existence of a passive Cl Ϫ conductance through the epithelial cells (13), which forms a simple shunt of PD. If the thickened dysplastic epithelium, possibly produced by a hyperplasia of the basal cells (6), did block this Cl Ϫ specific pathway, then the present results of the bronchitic change in basic parameters could be explained more reliably.…”

“…Since rabbit airway has essentially no submucosal glands (18), we can exclude the possible contributions of these glands to Isc across airway epithelium in the presence of secretagogues. Furthermore, rabbit tracheal epithelium is primarily absorptive, a characteristic that is similar to that of human (13,14,19).…”

“…To address this issue, we used an SO 2 -exposed rabbit as a model for bronchitic airway, because the bioelectric properties of rabbit trachea have been well characterized (13,14) and, also, because the methodology for preparing a bronchitic rabbit has been adequately established (15). Moreover, rabbit trachea has several advantages as a model for epithelial ion transport.…”

“…On the other hand, this type of epithelium has been shown to have no Isc response to ␤ -agonists or agents that raise cellular cyclic adenosine 3 Ј ,5 Ј -monophosphate (cAMP) (13,14,19), although it possesses ␤ -adrenergic receptors as well as an ability to increase the cellular level of cAMP in the presence of epinephrine, isoproterenol, or forskolin (20,21). The electric refractoriness of the freshly isolated rabbit trachea to isoproterenol and other cAMP-mediated agents was also confirmed in our previous study, and extracellular ATP was found to elicit a transient increase in Isc that was carried by Cl Ϫ , probably via P 2u -receptor (22).…”