title: Sustained depolarization and ADP-ribose activate a common ionic current in rat peritoneal macrophages.
abstract: Phagocytosis is associated with large changes in the membrane potential of macrophages, but the functional significance of this is unknown. Whole cell recordings were made from rat peritoneal macrophages. Sustained (>30 s) depolarization of the cells progressively activated a conductance that remained high (several nanoSeimens) for several tens of seconds. This current: 1) was linearly dependent on potential between -100 and +50 mV; 2) reversed close to 0 mV in a physiological external solution; 3) could also be carried in part by N-methyl-D-glucamine (P(NMDG)/P(Na) 0.7), chloride (P(Cl)/P(Na) 0.5), or calcium (P(Ca)/P(Na) 1.3); and 4) was blocked by intracellular ATP (5 mM) or ADP (10 mM) and by extracellular lanthanum (half-maximal concentration 1 mM). A current with all the same properties was recorded in cells when the intracellular solution contained ADP-ribose (10-300 micro M) or beta-NAD (1 mM) (but not any other nucleotide analogs tested). The results suggest that prolonged depolarization leads to an increased intracellular level of ADP-ribose, which in turn activates this nonselective conductance(s).
authors.affiliation: Institute of Molecular Physiology, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Brice
authors.initials: B
authors.lastname: Campo
authors.forename: Annmarie
authors.initials: A
authors.lastname: Surprenant
authors.forename: R Alan
authors.initials: RA
authors.lastname: North
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000378:metabolism; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000378:metabolism; D013113:Spin Labels; D013859:Thiocarbamates / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D018118:Chloride Channels; D007473:Ion Channels; D015222:Sodium Channels; D013113:Spin Labels; D013859:Thiocarbamates; D000246:Adenosine Diphosphate Ribose; D013012:Sorbitol; D007811:Lanthanum; C041262:N-methyl-D-glucamine dithiocarbamate