Sustained depolarization and ADP-ribose activate a common ionic current in rat peritoneal macrophages.
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).
Campo
Brice
B
Institute of Molecular Physiology, University of Sheffield, Sheffield, United Kingdom.
Surprenant
Annmarie
A
North
R Alan
RA
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
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