The goal of these studies is to identify the ionic currents that underlie salivary gland ductal function and to elucidate the intracellular factors that regulate these currents. The approach .Is to use the electrophysiological technique of patch clamping in order to complement and extend findings made using radiotracer techniques. The hypotheses to be tested are derived from results obtained in our preliminary studies, and from previous electrophysiological studies of salivary gland acinar cells, and generally test whether the same ionic currents and current regulating mechanisms present in acinar cells are also present in ductal cells. The studies utilize whole-cell current measurements from unstimulated and muscarinically stimulated HSG-PA tissue culture cells, and single channel current measurements on excised membrane patches from these cells. The whole-cell current studies allow analysis and characterization of resting cell membrane conduc- tances as well as effects of various intracellular agents involved in cell signaling such as G-proteins, IP3, Ca ion concentrations, protein kinase C and calmodulin. The single channel current studies will allow a definitive characterization of the potassium (and possibly the Cl) channels present in these cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009812-02
Application #
3223528
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1991-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Dentistry
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Fatherazi, S; Izutsu, K T; Martinez, J R (1996) Absence of acetylcholine- and ionomycin-activated Cl- currents in submandibular cells of early postnatal rats. Pflugers Arch 433:116-22
Izutsu, K T; Fatherazi, S; Belton, C M et al. (1996) Mycoplasma orale infection affects K+ and Cl- currents in the HSG salivary gland cell line. In Vitro Cell Dev Biol Anim 32:361-5
Lamont, R J; Chan, A; Belton, C M et al. (1995) Porphyromonas gingivalis invasion of gingival epithelial cells. Infect Immun 63:3878-85
Izutsu, K T; Fatherazi, S; Wellner, R B et al. (1994) Characteristics and regulation of a muscarinically activated K current in HSG-PA cells. Am J Physiol 266:C58-66
Fatherazi, S; Izutsu, K T; Wellner, R B et al. (1994) Hypotonically activated chloride current in HSG cells. J Membr Biol 142:181-93
Izutsu, K T; Oda, D; Yang, J (1993) A K+ conductance can be transiently activated in HSG-PA cells. Crit Rev Oral Biol Med 4:449-53