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 for salivary gland duct cells) after muscarinic receptor activation or exposure to known signaling agents. Exposure to carbachol or oxotremorine M produced large and often oscillatory increases in outward current whose reversal potentials indicated a K current. The current was sensitive to extracellular atropine, charybdotoxin, and quinine, but not apamin, and to 1,2-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-trisphosphate (IP3) or heparin in the pipette and by extracellular Ca ionophores. Tetraethylammonium indirectly inhibited the response via the muscarinic receptor. Fura 2 in cell suspensions showed that muscarinic agonists increased cytosolic Ca ion concentration ([Ca2+]i) five- to sevenfold, and measurements with indo 1 in individual cells showed that the oscillatory changes in outward current were tightly correlated with parallel changes in [Ca2+]i. The results indicate that muscarinic receptor stimulation of HSG-PA cells activates Ca(2+)-activated K channels through a signaling pathway involving a G protein, IP3 production, and increased [Ca2+]i levels. These findings are similar to those in salivary gland acinar cells.
Izutsu
K T
KT
Department of Oral Biology, School of Dentistry, University of Washington, Seattle 98195.
Fatherazi
S
S
Wellner
R B
RB
Herrington
J
J
Belton
C M
CM
Oda
D
D
D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D004594:Electrophysiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D010095:Oxotremorine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*; D026902:Potassium Channel Blockers; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D010277:Parasympathomimetics; D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010095:Oxotremorine; D019789:Tetraethylammonium; D002217:Carbachol; D011188:Potassium; D002118:Calcium