Autonomic stimulation of short circuit current in swine trachea

Autonomic stimulation of ionic fluxes was studied in tracheal epithelium of weanling swine by measuring short circuit current (ISC) in an Ussing chamber. Basal currents were predominantly secretory since 0.1 mM diphenylamine 2-carboxylic acid (DPC) reduced currents by twice as much as did 10 microM amiloride. Both acetylcholine (ACh) and isoproterenol (ISO) produced a sustained increase in ISC, with the EC50 for ISO being 149 nM and for ACh being 500 nM. In both cases, the induced currents were predominantly secretory since 10 microM amiloride had little effect on either agonist-induced delta ISC whereas DPC inhibited the ISO- and ACh-induced delta ISC's by 30% and 47% respectively. However, responses to ACh and ISO could be distinguished on three grounds. [1] An anatomic gradient existed with smaller responses to agonists being observed towards the distal trachea. The ISO-induced currents showed a steeper gradient than the ACh-induced currents. [2] In single tissue samples, the size of the ISO-induced delta ISC was not correlated with the size of the ACh-induced delta ISC. [3] The magnitude of the delta ISC induced by ACh was unaffected by a concomitant stimulation of ISC by ISO. Thus, ACh-induced secretion was independent of ISO-induced secretion, and likely occurred in different cell types.