title: CNS neurons express two distinct plasma membrane electron transport systems implicated in neuronal viability.
abstract: Trans-plasma membrane electron transport is critical for maintaining cellular redox balance and viability, yet few, if any, investigations have studied it in intact primary neurons. In this investigation, extracellular reduction of 2,6-dichloroindophenol (DCIP) and ferricyanide (FeCN) were measured as indicators of trans-plasma membrane electron transport by chick forebrain neurons. Neurons readily reduced DCIP, but not FeCN unless CoQ(1), an exogenous ubiquinone analog, was added to the assays. CoQ(1) stimulated FeCN reduction in a dose-dependent manner but had no effect on DCIP reduction. Reduction of both substrates was totally inhibited by epsilon-maleimidocaproic acid (MCA), a membrane-impermeant thiol reagent, and slightly inhibited by superoxide dismutase. Diphenylene iodonium, a flavoenzyme inhibitor, completely inhibited FeCN reduction but had no affect on DCIP reduction, suggesting that these substrates are reduced by distinct redox pathways. The relationship between plasma membrane electron transport and neuronal viability was tested using the inhibitors MCA and capsaicin. MCA caused a dose-dependent decline in neuronal viability that closely paralleled its inhibition of both reductase activities. Similarly capsaicin, a NADH oxidase inhibitor, induced a rapid decline in neuronal viability. These results suggest that trans-plasma membrane electron transport helps maintain a stable redox environment required for neuronal viability.
authors.affiliation: Institute of Arctic Biology, University of Alaska, Fairbanks, Alaska, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Wright
authors.forename: T B
authors.initials: TB
authors.lastname: Kuhn
mesh_terms: D015086:2,6-Dichloroindophenol / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D020134:Catalytic Domain / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002642:Chick Embryo; D001728:Dicumarol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005292:Ferricyanides / Q000032:analysis / Q000378:metabolism; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D012402:Rotenone / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014451:Ubiquinone / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005292:Ferricyanides; D009097:Multienzyme Complexes; D009861:Onium Compounds; D013439:Sulfhydryl Reagents; D014475:Uncoupling Agents; D012402:Rotenone; D014451:Ubiquinone; C007931:hexacyanoferrate III; C007517:diphenyleneiodonium; D001728:Dicumarol; D015086:2,6-Dichloroindophenol; D013482:Superoxide Dismutase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; C025203:Ubiquinone Q1; D002211:Capsaicin