Effect of ion transport inhibitors and methacholine on short-circuit current of isolated guinea pig nasal epithelium

To clarify the ion/water secretion mechanism in the nasal epithelial cells, the Ussing chamber method was applied to the nasal mucosa isolated from guinea pigs. The preparation, which contained surface epithelial cells, showed a small but consistent potential difference between mucosal and submucosal sides (mucosal surface negative to submucosa). The short-circuit current (Isc) across the epithelial layer was measured, and the effects of Na+ and/or Cl- transport inhibitors and methacholine (MCh) on Isc were analyzed. The basal Isc was almost totally suppressed by the combined application of amiloride (Na+ transport inhibitor) and low-Cl- Krebs Ringer (KR) solution or solutions containing Cl- transport inhibitors (furosemide or DPC). The application of MCh elicited triphasic Isc responses, i.e., initial transient increase (phase 1) followed by a small decrease (phase 2) and further sustained increase (phase 3) in Isc. A possible ionic mechanism underlying phase 1 and 3 responses was analyzed. The Phase 1 response was greatly reduced by low-Cl- KR solution or furosemide but not influenced by amiloride. The Phase 3 response was augmented by amiloride and suppressed by low-Cl- KR solution, furosemide or DPC. These findings indicated that the basal Isc was associated with Cl- secretion and/or Na+ absorption across epithelial cells under short-circuit condition and that MCh increased Isc probably via enhancing Cl- secretion in the nasal surface epithelial cell.