title: Angiotensin II induces oscillations of intracellular calcium and blocks anomalous inward rectifying potassium current in mouse renal juxtaglomerular cells.
abstract: Simultaneous patch-clamp and fura-2 measurements were used to investigate the electrical properties and receptor-mediated changes of intracellular calcium in renal juxtaglomerular cells. Here we report the presence of voltage-activated inward and outward rectifying potassium currents and the inhibition of the anomalous inward rectifying potassium current by angiotensin II (ANG-II). This action of ANG-II was mimicked by guanosine 5'-[gamma-thio]triphosphate but not by cAMP, cGMP, inositol 1,4,5-trisphosphate, or phorbol ester, suggesting that ANG-II inhibits the potassium channel directly by means of a guanine nucleotide-binding regulatory protein or by means of an unusual type of second messenger. Blocking of the inward rectifier was paralleled by membrane depolarization, but we obtained no evidence for calcium entry due to voltage-gated calcium channels in juxtaglomerular cells. Instead, under voltage clamp, ANG-II and guanosine 5'-[gamma-thio]triphosphate induced release of calcium from intracellular stores followed by a sustained phase of transmembrane calcium influx and oscillations of intracellular Ca2+ concentrations. Changes in intracellular Ca2+ concentrations were found to depend on the extracellular Ca concentration--i.e., the sustained elevation was abolished in absence of extracellular Ca, and the frequency of repetitive calcium release was directly related to the extracellular concentration of calcium. Moreover, an elevation of extracellular Ca concentration by itself induced release of intracellular calcium in the absence of other stimuli. Changes in intracellular Ca2+ concentrations were accompanied by prominent calcium-activated chloride currents, and this mechanism is inferred to be responsible for the inhibitory role of calcium in renin secretion. Intracellular application of cAMP but no cGMP inhibited ANG-II and guanosine 5'-[gamma-thio]triphosphate induced calcium mobilization in juxtaglomerular cells, being consistent with the facilitatory effects of elevated cAMP levels of renin release. The frequency of ANG-II induced oscillations was also markedly attenuated at depolarized membrane potentials suggesting effective negative feedback control of ANG-II-induced depolarization on repetitive Ca2+ transients induced by the hormone.
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Federal Republic of Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kurtz
authors.forename: R
authors.initials: R
authors.lastname: Penner
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004553:Electric Conductivity; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D015221:Potassium Channels; D013873:Thionucleotides; D000804:Angiotensin II; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D002118:Calcium