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. 1971 May;215(1):199–222. doi: 10.1113/jphysiol.1971.sp009465

Actions of dinitrophenol and some other metabolic inhibitors on cortical neurones

J M Godfraind, H Kawamura, K Krnjević, R Pumain
PMCID: PMC1331874  PMID: 5579652

Abstract

1. In cats under methoxyflurane, DNP and other metabolic inhibitors were tested on cortical neurones by iontophoresis from micropipettes.

2. DNP, dinitro-o-cresol, iodoacetate, pentachlorophenol and oligomycin (uncouplers or inhibitors of oxidative phosphorylation), as well as moderate anoxia, blocked selectively and reversibly spontaneous firing and discharges evoked by ACh; responses evoked by glutamate were facilitated by moderate doses of DNP and blocked only by large amounts.

3. Azide, cyanide, ouabain and strophanthidine had a mainly excitatory effect; the cardiac glycosides tended to depress more strongly responses to glutamate.

4. Intracellular observations showed that DNP causes a sharp fall in electrical excitability, associated with a hyperpolarization and fall in membrane resistance.

5. The hyperpolarizing action of DNP had a mean reversal level (EDNP) nearly 30 mV more negative than the resting potential; EDNP was identical with the mean reversal level for the depolarizing action of ACh, measured on the same cells.

6. DNP had its usual hyperpolarizing effect on neurones whose IPSPs had been made positive by raising the internal [Cl]; the mean EIPSP was over 30 mV more positive than EDNP.

7. It is concluded that DNP lowers excitability by raising the membrane conductance to K+ (gK) and that it blocks ACh responses selectively because ACh has a precisely opposite action on these neurones.

8. In the Discussion, it is suggested that the rise in gK is mediated by an increase in internal free Ca2+, caused by a slowing of mitochondrial activity, and that a similar mechanism may play a significant role in general anaesthesia.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carafoli E., Patriarca P., Rossi C. S. A comparative study of the role of mitochondria and the sarcoplasmic reticulum in the uptake and release of Ca++ by the rat diaphragm. J Cell Physiol. 1969 Aug;74(1):17–30. doi: 10.1002/jcp.1040740104. [DOI] [PubMed] [Google Scholar]
  2. Chalazonitis N. Selective actions of volatile anesthetics on synaptic transmission and autorhythmicity in single identifiable neurons. Anesthesiology. 1967 Jan-Feb;28(1):111–123. [PubMed] [Google Scholar]
  3. Dean P. M., Matthews E. K. Glucose-induced electrical activity in pancreatic islet cells. J Physiol. 1970 Sep;210(2):255–264. doi: 10.1113/jphysiol.1970.sp009207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dreifuss J. J., Kelly J. S., Krnjević K. Cortical inhibition and gamma-aminobutyric acid. Exp Brain Res. 1969;9(2):137–154. doi: 10.1007/BF00238327. [DOI] [PubMed] [Google Scholar]
  5. Glagoleva I. M., Liberman E. A., Khashaev Z. Kh. Vliianie razobshchitelei okislitel'nogo fosforilirovaniia na vykhod atsetilkholina iz nervnykh okonchanii. Biofizika. 1970 Jan-Feb;15(1):76–83. [PubMed] [Google Scholar]
  6. Godfraind J. M., Krnjević K., Pumain R. Unexpected features of the action of dinitrophenol on cortical neurones. Nature. 1970 Nov 7;228(5271):562–564. doi: 10.1038/228562a0. [DOI] [PubMed] [Google Scholar]
  7. HOLLANDER P. B., WEBB J. L. Metabolic aspects of the relationship between the contractility and membrane potentials of the rat atrium. Circ Res. 1956 Sep;4(5):618–626. doi: 10.1161/01.res.4.5.618. [DOI] [PubMed] [Google Scholar]
  8. Hopfer U., Lehninger A. L., Thompson T. E. Protonic conductance across phospholipid bilayer membranes induced by uncoupling agents for oxidative phosphorylation. Proc Natl Acad Sci U S A. 1968 Feb;59(2):484–490. doi: 10.1073/pnas.59.2.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. ITO M., OSHIMA T. THE ELECTROGENIC ACTION OF CATIONS ON CAT SPINAL MOTONEURONS. Proc R Soc Lond B Biol Sci. 1964 Nov 17;161:92–108. doi: 10.1098/rspb.1964.0082. [DOI] [PubMed] [Google Scholar]
  10. KERKUT G. A., THOMAS R. C. AN ELECTROGENIC SODIUM PUMP IN SNAIL NERVE CELLS. Comp Biochem Physiol. 1965 Jan;14:167–183. doi: 10.1016/0010-406x(65)90017-4. [DOI] [PubMed] [Google Scholar]
  11. KRAATZ H. G., TRAUTWEIN W. Die Wirkung von 2,4-Dinitrophenol (DNP) auf die neuromuskuläre Erregungsübertragung. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1957;231(5):419–439. [PubMed] [Google Scholar]
  12. Karahashi Y., Goldring S. Intracellular potentials from "idle" cells in cerebral cortex of cat. Electroencephalogr Clin Neurophysiol. 1966 Jun;20(6):600–607. doi: 10.1016/0013-4694(66)90024-1. [DOI] [PubMed] [Google Scholar]
  13. Kelly J. S., Krnjević K., Morris M. E., Yim G. K. Anionic permeability of cortical neurones. Exp Brain Res. 1969;7(1):11–31. doi: 10.1007/BF00236105. [DOI] [PubMed] [Google Scholar]
  14. Kelly J. S., Krnjević K., Yim G. K. Unresponsive cells in cerebral cortex. Brain Res. 1967 Dec;6(4):767–769. doi: 10.1016/0006-8993(67)90132-1. [DOI] [PubMed] [Google Scholar]
  15. Kobayashi H., Libet B. Actions of noradrenaline and acetylcholine on sympathetic ganglion cells. J Physiol. 1970 Jun;208(2):353–372. doi: 10.1113/jphysiol.1970.sp009125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kobayashi H., Libet B. Generation of slow postsynaptic potentials without increases in ionic conductance. Proc Natl Acad Sci U S A. 1968 Aug;60(4):1304–1311. doi: 10.1073/pnas.60.4.1304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Krnjević K., Pumain R., Renaud L. Effects of Ba2+ and tetraethylammonium on cortical neurones. J Physiol. 1971 May;215(1):223–245. doi: 10.1113/jphysiol.1971.sp009466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Krnjević K., Pumain R., Renaud L. The mechanism of excitation by acetylcholine in the cerebral cortex. J Physiol. 1971 May;215(1):247–268. doi: 10.1113/jphysiol.1971.sp009467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Krnjević K., Schwartz S. Some properties of unresponsive cells in the cerebral cortex. Exp Brain Res. 1967;3(4):306–319. doi: 10.1007/BF00237557. [DOI] [PubMed] [Google Scholar]
  20. Krnjević K., Schwartz S. The action of gamma-aminobutyric acid on cortical neurones. Exp Brain Res. 1967;3(4):320–336. doi: 10.1007/BF00237558. [DOI] [PubMed] [Google Scholar]
  21. Lehninger A. L., Carafoli E., Rossi C. S. Energy-linked ion movements in mitochondrial systems. Adv Enzymol Relat Areas Mol Biol. 1967;29:259–320. doi: 10.1002/9780470122747.ch6. [DOI] [PubMed] [Google Scholar]
  22. Lew V. L. Effect of intracellular calcium on the potassium permeability of human red cells. J Physiol. 1970 Feb;206(2):35P–36P. [PubMed] [Google Scholar]
  23. Liberman E. A., Topaly V. P. Perenos ionov cherez bimolekuliarnye membrany i klassifikatsiia pazobshchitelei okislitel'nogo fosforilirovaniia. Biofizika. 1968 Nov-Dec;13(6):1025–1035. [PubMed] [Google Scholar]
  24. Lust W. D., Robinson J. D. Calcium accumulation by isolated nerve ending particles from brain. I. The site of energy-dependent accumulation. J Neurobiol. 1969;1(3):303–316. doi: 10.1002/neu.480010306. [DOI] [PubMed] [Google Scholar]
  25. Nishi S., Soeda H., Koketsu K. Unusual nature of ganglionic slow EPSP studied by a voltage-clamp method. Life Sci. 1969 Jan 1;8(1):33–42. doi: 10.1016/0024-3205(69)90290-2. [DOI] [PubMed] [Google Scholar]
  26. Papahadjopoulos D., Watkins J. C. Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals. Biochim Biophys Acta. 1967 Sep 9;135(4):639–652. doi: 10.1016/0005-2736(67)90095-8. [DOI] [PubMed] [Google Scholar]
  27. Phillis J. W., York D. H. Cholinergic inhibition in the cerebral cortex. Brain Res. 1967 Aug;5(4):517–520. doi: 10.1016/0006-8993(67)90025-x. [DOI] [PubMed] [Google Scholar]
  28. Pollen D. A., Lux H. D. Conductance changes during inhibitory postsynaptic potentials in normal and strychninized cortical neurons. J Neurophysiol. 1966 May;29(3):369–381. doi: 10.1152/jn.1966.29.3.369. [DOI] [PubMed] [Google Scholar]
  29. QUASTEL J. H. Biochemical aspects of narcosis. Curr Res Anesth Analg. 1952 May-Jun;31(3):151–163. [PubMed] [Google Scholar]
  30. RANDIC M., SIMINOFF R., STRAUGHAN D. W. ACETYLCHOLINE DEPRESSION OF CORTICAL NEURONS. Exp Neurol. 1964 Mar;9:236–242. doi: 10.1016/0014-4886(64)90020-2. [DOI] [PubMed] [Google Scholar]
  31. Sato M., Austin G. M., Yai H. Increase in permeability of the postsynaptic membrane to potassium produced by 'nembutal'. Nature. 1967 Sep 30;215(5109):1506–1508. doi: 10.1038/2151506a0. [DOI] [PubMed] [Google Scholar]
  32. Waddell W. J., Bates R. G. Intracellular pH. Physiol Rev. 1969 Apr;49(2):285–329. doi: 10.1152/physrev.1969.49.2.285. [DOI] [PubMed] [Google Scholar]
  33. Whittam R. Control of membrane permeability to potassium in red blood cells. Nature. 1968 Aug 10;219(5154):610–610. doi: 10.1038/219610a0. [DOI] [PubMed] [Google Scholar]

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