IMPORTANCE OF BASOLATERAL K- SECRETION IN MURINE NASAL AND COLONIC EPITHELIA( CONDUCTANCE IN MAINTAINING CL)

1.Epithelia lining the nasal passages and descending colon of wild-typ e and cystic fibrosis (CF) mice were examined by the short-circuit cur rent technique. Additionally: intracellular Ca2+ ion determinations we re made in nasal epithelial cells. Forskolin produced anion secretory currents in wild-type and CF nasal epithelia. It produced similar effe cts in mild-type colonic epithelia, but not in colonic epithelia from CF mice. 2. After electrogenic Na+ transport was blocked with amilorid e and electrogenic Cl- secretion was stimulated with forskolin, the ab ility of K+ channel blockers to inhibit the forskolin-induced Cl- curr ent was determined. The order of efficiency for nasal epithelium was: Ba2+ > clofilium >>> TEA = azimilide >>> nyl-N-methylamino)-3-hydroxy- 2,2-dimethyl-chromane (293B)= charybdotoxin, whereas for the colonic e pithelium the order was: Ba2+ = 293B >>> azimilide = TEA >>> clofilium = charybdotoxin. 3. 1-Ethyl-2-benzimdazolinone (1-EBIO) was able to g enerate large Cl--secretory currents in colonic epithelia which were p artially sensitive to charybdotoxin, with the remaining current being inhibited by 293B. In nasal epithelia 1-EBIO produced only a small tra nsient effect on current. 4. Forskolin released intracellular Ca2+ in nasal epithelial cells; this activity was attenuated when more powerfu l Ca2+-releasing agents were applied first. 5. It is concluded that an action on basolateral cAMP-sensitive K+ channels is an important dete rminant of the maintained responses to forskolin in nasal and colonic epithelia, in addition to the effects on the cystic fibrosis transmemb rane conductance regulator (CFTR) in the apical membrane. In CF nasal epithelia the activation of calcium-activated chloride channels (CACs) substitutes for the effect on CFTR. On the basis of the different ord ers of potency of the blocking agents and the differential response to 1-EBIO it is concluded that the cAMP-sensitive K+ channels are differ ent in the airways and the gut.