A forskolin-activated Cl- current in mouse mandibular duct cells

Area of Science:

• Physiology
• Ion Channels
• Salivary Gland Biology

Background:

• Unstimulated granular duct cells of the mouse mandibular gland exhibit a hyperpolarization-activated chloride (Cl-) conductance similar to ClC-2.
• This suggests the presence of multiple Cl- transport mechanisms within these cells.

Purpose of the Study:

• To identify and characterize a second whole-cell Cl- conductance activated by stimulation in mouse mandibular gland granular duct cells.
• To determine the properties and potential identity of this forskolin-stimulated Cl- conductance.

Main Methods:

• Electrophysiological recordings (whole-cell patch-clamp) were used to measure Cl- currents.
• Forskolin and 1,9-dideoxyforskolin were employed to stimulate specific conductances.
• Anion permeability and conductance sequences were determined.
• Pharmacological agents (diphenylamine-2-carboxylate, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, glibenclamide, norepinephrine, propranolol) were used to probe channel characteristics and activation pathways.

Main Results:

• Forskolin, but not 1,9-dideoxyforskolin, activated a linear, non-voltage-activated Cl- conductance.
• The anion permeability sequence was Br- > NO3- > Cl- > I-, and the conductance sequence was Cl- > NO3- > Br- > I-.
• Norepinephrine activated this conductance via beta-adrenergic receptors, with effects inhibited by propranolol.
• Diphenylamine-2-carboxylate attenuated the current, while other inhibitors had no effect.

Conclusions:

• The adrenergically evoked conductance in mouse mandibular gland granular duct cells is attributed to the cystic fibrosis transmembrane conductance regulator (CFTR).
• CFTR is expressed in salivary duct cells and likely contributes to the modulation of NaCl absorption by beta-adrenergic agonists.