title: A zinc-dependent Cl- current in neuronal somata.
abstract: Extracellular Zn2+ modulates current passage through voltage- and neurotransmitter-gated ion channels, at concentrations less than, or near, those produced by release at certain synapses. Electrophysiological effects of cytoplasmic Zn2+ are less well understood, and effects have been observed at concentrations that are orders of magnitude greater than those found in resting and stimulated neurons. To examine whether and how neurons are affected by lower levels of cytoplasmic Zn2+, we tested the effect of Zn2+-selective chelators, Zn2+-preferring ionophores, and exogenous Zn2+ on neuronal somata during whole-cell patch-clamp recordings. We report here that cytoplasmic zinc facilitates the downward regulation of a background Cl- conductance by an endogenous protein kinase C (PKC) in fish retinal ganglion cell somata and that this regulation is maintained if nanomolar levels of free Zn2+ are available. This regulation has not been described previously in any tissue, as other Cl- currents have been described as reduced by PKC alone, reduced by Zn2+ alone, or reduced by both independently. Moreover, control of cation currents by a zinc-dependent PKC has not been reported previously. The regulation we have observed thus provides the first electrophysiological measurements consistent with biochemical measurements of zinc-dependent PKC activity in other systems. These results suggest that contributions of background Cl- conductances to electrical properties of neurons are susceptible to modulation.
authors.affiliation: Section of Neurobiology, Physiology, and Behavior, University of California, Davis, 95616-8519, USA.
authors.forename: T
authors.initials: T
authors.lastname: Tabata
authors.forename: A T
authors.initials: AT
authors.lastname: Ishida
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002412:Cations / Q000378:metabolism / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006054:Goldfish; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D007476:Ionophores / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002412:Cations; D002614:Chelating Agents; D002712:Chlorides; D007211:Indoles; D007473:Ion Channels; D007476:Ionophores; D008301:Maleimides; D009281:Naphthalenes; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000242:Cyclic AMP; D011493:Protein Kinase C; C058819:calphostin C; D015032:Zinc; C088060:bisindolylmaleimide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium