A Forskolin-activated Cl- Current in Mouse Mandibular Duct Cells

We have previously shown that unstimulated granular duct cells of mouse mandibular gland contain a hyperpolarization-activated Cl- conductance with characteristics resembling the hyperpolarization-activated volume-sensitive Cl- channel (ClC-2). We now show that stimulation of these cells with forskolin, but not 1,9-dideoxyforskolin, activates a second whole cell Cl- conductance with properties resembling the cystic fibrosis transmembrane conductance regulator (CFTR). This conductance has 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 attenuated 65% by 1 mmol/l diphenylamine-2-carboxylate but is not affected by 0.1 mmol/l4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid or 0.1 mmol/l glibenclamide. The current can be activated by norepinephrine (1 mumol/l), evidently acting via beta-adrenergic receptors, since the effect of norepinephrine is inhibited by propranolol (1 mumol/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-adrenergic agonists modulate NaCl absorption by salivary ducts.