CHARACTERISTICS AND REGULATION OF A MUSCARINICALLY ACTIVATED K-CURRENT IN HSG-PA CELLS

Whole cell currents were measured in HSG-PA cells (a proposed model fo r salivary gland duct cells) after muscarinic receptor activation or e xposure to known signaling agents. Exposure to carbachol or oxotremori ne M produced large and often oscillatory increases in outward current whose reversal potentials indicated a K current. The current was sens itive to extracellular atropine, charybdotoxin, and quinine, but not a pamin, and to ,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in the pipette. The response was prolonged or increased by guanosine 5 '-O-(3-thiotriphosphate) and mimicked by D-myo-inositol 1,4,5-trisphos phate (IP3) or heparin in the pipette and by extracellular Ca ionophor es. Tetraethylammonium indirectly inhibited the response via the musca rinic receptor. Fura 2 in cell suspensions showed that muscarinic agon ists increased cytosolic Ca ion concentration ([Ca2+](i)) five to seve nfold, and measurements with indo 1 in individual cells showed that th e oscillatory changes in outward current were tightly correlated with parallel changes in [Ca2+](i). The results indicate that muscarinic re ceptor stimulation of HSG-PA cells activates Ca2+-activated K channels through a signaling pathway involving a G protein, IP3 production, an d increased [Ca2+](i) levels. These findings are similar to those in s alivary gland acinar cells.