A FORSKOLIN-ACTIVATED CL- CURRENT IN MOUSE MANDIBULAR DUCT CELLS

We have previously shown that unstimulated granular duct cells of mous e mandibular gland contain a hyperpolarization-activated Cl- conductan ce with characteristics resembling the hyperpolarization-activated vol ume-sensitive Cl- channel (ClC-2). We now show that stimulation of the se cells with forskolin, but not 1,9-dideoxyforskolin, activates a sec ond whole cell Cl- conductance with properties resembling the cystic f ibrosis transmembrane conductance regulator (CFTR). This conductance h as a linear current-voltage relation and is not voltage activated. Its anion permeability sequence is Br- (1.96) > NO3- (1.36) > Cl- (1) > I - (0.44), and its conductance sequence is Cl- (1) > NO3- (0.66) > Br- (0.34) > I- (0.21). The current carried by this conductance is attenua ted 65% by 1 mmol/l diphenylamine-2-carboxylate but is not affected by 0.1 mmol/l 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid or 0.1 mmol/l glibenclamide. The current can be activated by norepinephrine ( 1 mu mol/l), evidently acting via beta-adrenergic receptors, since the effect of norepinephrine is inhibited by propranolol (1 mu mol/l). We conclude that this adrenergically evoked conductance is due to CFTR, which has previously been shown to be expressed in salivary duct cells , and suggest that it may form part of the mechanism by which beta-adr energic agonists modulate NaCl absorption by salivary ducts.