title: Multiple signaling pathways for Cl(-)-dependent depolarization of mesangial cells: role of Ca2+, PKC, and G proteins.
abstract: We have previously reported that vasopressin activates chloride channels, leading to depolarization of glomerular mesangial cells via both calcium-dependent and calcium-independent pathways (S.G. Kremer, W.V. Breuer, and K. L. Skorecki, J. Cell. Physiol. 138: 97-105, 1989). However, the calcium-independent pathways were not defined. Using fluorescent probes, we now demonstrate that activation of protein kinase C (PKC) results in cellular depolarization in the absence of a calcium signal. This depolarization is also mediated by an enhanced conductance to chloride. Downregulation of PKC partially attenuated but did not abolish the depolarization response to vasopressin. Depolarization persisted when, in addition, calcium responses were also abolished and prostaglandin production was eliminated, suggesting an additional pathway for depolarization. G protein activation by aluminum fluoride also resulted in cellular depolarization mediated by an enhanced conductance to chloride, which persisted when calcium and PKC-signaling pathways were eliminated. This suggests the presence of a calcium- and PKC-independent pathway for G protein-mediated chloride-dependent depolarization. These findings point to the presence of at least three separate signaling pathways available for the activation of mesangial cell chloride channels, i.e., calcium, PKC, and a G protein.
authors.affiliation: Department of Medicine and Pediatrics, University of Toronto, Ontario, Canada.
authors.forename: S G
authors.initials: SG
authors.lastname: Kremer
authors.forename: W
authors.initials: W
authors.lastname: Zeng
authors.forename: S
authors.initials: S
authors.lastname: Sridhara
authors.forename: K L
authors.initials: KL
authors.lastname: Skorecki
mesh_terms: D000535:Aluminum / Q000494:pharmacology / Q000502:physiology; D017607:Aluminum Compounds; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D002712:Chlorides / Q000502:physiology*; D015536:Down-Regulation; D004594:Electrophysiology; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D008297:Male; D009712:Nucleotides, Cyclic / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D009712:Nucleotides, Cyclic; D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D000535:Aluminum; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride