Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1979 Jun;291:507–530. doi: 10.1113/jphysiol.1979.sp012828

Inactivation of delayed outward current in molluscan neurone somata.

R W Aldrich Jr, P A Getting, S H Thompson
PMCID: PMC1280916  PMID: 480244

Abstract

1. Inactivation of delayed outward current was studied by voltage clamp of isolated neurone somata of the molluscs Archidoris and Anisodoris. During prolonged voltage clamp steps in normal artificial sea water delayed outward current rises to a peak and then declines to a non-zero steady-state. During repetitive clamp pulses at repetition rates slower than 2/sec, the amplitude of peak outward current in the second pulse is commonly less than the amplitude at the end of the preceding pulse, giving the impression of continued inactivation during the repolarized interval. We have termed this property cumulative inactivation. 2. Two components of delayed outward current were separated using tetraethyl ammonium ions (TEA) and cobalt ions (Co). External TEA blocks 90% of a voltage and time dependent outward current termed K current (IK). External Co blocks 85% of a Ca activated delayed outward current termed Ca current (ICa does not inactivate during prolonged or repetitive voltage clamp pulses. IK, however, inactivates during prolonged voltage clamp steps and shows cumulative inactivation during repetitive voltage clamp pulses. 3. Inactivation of IK is voltage and time dependent and does not require influx of Ca ions. 4. As measured by a prepulse method, the onset of inactivation is characterized by a two time constant process. Fast inactivation occurs with a time course comparable to the rate of rise of outward current and can account for 90% of total inactivation. 5. Recovery from inactivation is slow with a time constant approximately an order of magnitude slower than the onset of inactivation. 6. The current-voltage (I-V) curve for peak IK can be N-shaped, with a region of negative slope resistance in the range of +30 to +80 mV. The I-V curve for steady-state IK, however, shows little or no tendency to form a local maximum. 7. The pattern of delayed outward current varies considerably between cells. A major contributing factor to this variability appears to be the relative contributions of ICa and IK to delayed outward current.

Full text

PDF
507

Selected References

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

  1. Adams D. J., Gage P. W. Gating currents associated with sodium and calcium currents in an Aplysia neuron. Science. 1976 May 21;192(4241):783–784. doi: 10.1126/science.1265479. [DOI] [PubMed] [Google Scholar]
  2. Akaike N., Lee K. S., Brown A. M. The calcium current of Helix neuron. J Gen Physiol. 1978 May;71(5):509–531. doi: 10.1085/jgp.71.5.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aldrich R. W., Jr, Getting P. A., Thompson S. H. Mechanism of frequency-dependent broadening of molluscan neurone soma spikes. J Physiol. 1979 Jun;291:531–544. doi: 10.1113/jphysiol.1979.sp012829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Armstrong C. M. Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons. J Gen Physiol. 1969 Nov;54(5):553–575. doi: 10.1085/jgp.54.5.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Armstrong C. M. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol. 1971 Oct;58(4):413–437. doi: 10.1085/jgp.58.4.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chandler W. K., Meves H. Evidence for two types of sodium conductance in axons perfused with sodium fluoride solution. J Physiol. 1970 Dec;211(3):653–678. doi: 10.1113/jphysiol.1970.sp009298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Connor J. A., Stevens C. F. Inward and delayed outward membrane currents in isolated neural somata under voltage clamp. J Physiol. 1971 Feb;213(1):1–19. doi: 10.1113/jphysiol.1971.sp009364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Connor J. A., Stevens C. F. Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma. J Physiol. 1971 Feb;213(1):31–53. doi: 10.1113/jphysiol.1971.sp009366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Connor J. A., Stevens C. F. Voltage clamp studies of a transient outward membrane current in gastropod neural somata. J Physiol. 1971 Feb;213(1):21–30. doi: 10.1113/jphysiol.1971.sp009365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Connor J. A. Time course separation of two inward currents in molluscan neurons. Brain Res. 1977 Jan 7;119(2):487–492. doi: 10.1016/0006-8993(77)90330-4. [DOI] [PubMed] [Google Scholar]
  11. Courtney K. R. Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA. J Pharmacol Exp Ther. 1975 Nov;195(2):225–236. [PubMed] [Google Scholar]
  12. Dionne V. E., Stevens C. F. Voltage dependence of agonist effectiveness at the frog neuromuscular junction: resolution of a paradox. J Physiol. 1975 Oct;251(2):245–270. doi: 10.1113/jphysiol.1975.sp011090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Eaton D. C. Potassium ion accumulation near a pace-making cell of Aplysia. J Physiol. 1972 Jul;224(2):421–440. doi: 10.1113/jphysiol.1972.sp009903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Eckert R., Lux H. D. A voltage-sensitive persistent calcium conductance in neuronal somata of Helix. J Physiol. 1976 Jan;254(1):129–151. doi: 10.1113/jphysiol.1976.sp011225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eckert R., Lux H. D. Calcium-dependent depression of a late outward current in snail neurons. Science. 1977 Jul 29;197(4302):472–475. doi: 10.1126/science.17921. [DOI] [PubMed] [Google Scholar]
  16. Eckert R., Tillotson D. Potassium activation associated with intraneuronal free calcium. Science. 1978 Apr 28;200(4340):437–439. doi: 10.1126/science.644308. [DOI] [PubMed] [Google Scholar]
  17. Eckert R., Tillotson D., Ridgway E. B. Voltage-dependent facilitation of Ca2+ entry in voltage-clamped, aequorin-injected molluscan neurons. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1748–1752. doi: 10.1073/pnas.74.4.1748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ehrenstein G., Gilbert D. L. Slow changes of potassium permeability in the squid giant axon. Biophys J. 1966 Sep;6(5):553–566. doi: 10.1016/S0006-3495(66)86677-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. FRANKENHAEUSER B., HODGKIN A. L. The after-effects of impulses in the giant nerve fibres of Loligo. J Physiol. 1956 Feb 28;131(2):341–376. doi: 10.1113/jphysiol.1956.sp005467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Geduldig D., Gruener R. Voltage clamp of the Aplysia giant neurone: early sodium and calcium currents. J Physiol. 1970 Nov;211(1):217–244. doi: 10.1113/jphysiol.1970.sp009276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gola M. Neurones à ondes-salves des mollusques. Variations cycliques lentes des conductances ioniques. Pflugers Arch. 1974;352(1):17–36. doi: 10.1007/BF01061947. [DOI] [PubMed] [Google Scholar]
  22. HAGIWARA S., KUSANO K., SAITO N. Membrane changes of Onchidium nerve cell in potassium-rich media. J Physiol. 1961 Mar;155:470–489. doi: 10.1113/jphysiol.1961.sp006640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. HAGIWARA S., SAITO N. Voltage-current relations in nerve cell membrane of Onchidium verruculatum. J Physiol. 1959 Oct;148:161–179. doi: 10.1113/jphysiol.1959.sp006279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. HODGKIN A. L., HUXLEY A. F. The components of membrane conductance in the giant axon of Loligo. J Physiol. 1952 Apr;116(4):473–496. doi: 10.1113/jphysiol.1952.sp004718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hagiwara S. Ca spike. Adv Biophys. 1973;4:71–102. [PubMed] [Google Scholar]
  27. Heyer C. B., Lux H. D. Control of the delayed outward potassium currents in bursting pace-maker neurones of the snail, Helix pomatia. J Physiol. 1976 Nov;262(2):349–382. doi: 10.1113/jphysiol.1976.sp011599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Heyer C. B., Lux H. D. Properties of a facilitating calcium current in pace-maker neurones of the snail, Helix pomatia. J Physiol. 1976 Nov;262(2):319–348. doi: 10.1113/jphysiol.1976.sp011598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kostyuk P. G., Krishtal O. A., Pidoplichko V. I. Effect of internal fluoride and phosphate on membrane currents during intracellular dialysis of nerve cells. Nature. 1975 Oct 23;257(5528):691–693. doi: 10.1038/257691a0. [DOI] [PubMed] [Google Scholar]
  30. Lux H. D., Eckert R. Inferred slow inward current in snail neurones. Nature. 1974 Aug 16;250(467):574–576. doi: 10.1038/250574a0. [DOI] [PubMed] [Google Scholar]
  31. Lux H. D., Heyer C. B. An aequorin study of a facilitating calcium current in bursting pacemaker neurons of Helix. Neuroscience. 1977;2(4):585–592. doi: 10.1016/0306-4522(77)90054-9. [DOI] [PubMed] [Google Scholar]
  32. Meech R. W. Calcium-dependent potassium activation in nervous tissues. Annu Rev Biophys Bioeng. 1978;7:1–18. doi: 10.1146/annurev.bb.07.060178.000245. [DOI] [PubMed] [Google Scholar]
  33. Meech R. W., Standen N. B. Potassium activation in Helix aspersa neurones under voltage clamp: a component mediated by calcium influx. J Physiol. 1975 Jul;249(2):211–239. doi: 10.1113/jphysiol.1975.sp011012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nakajima S. Analysis of K inactivation and TEA action in the supramedullary cells of puffer. J Gen Physiol. 1966 Mar;49(4):629–640. doi: 10.1085/jgp.49.4.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nakajima S., Kusano K. Behavior of delayed current under voltage clamp in the supramedullary neurons of puffer. J Gen Physiol. 1966 Mar;49(4):613–628. doi: 10.1085/jgp.49.4.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Neher E., Lux H. D. Properties of somatic membrane patches of snail neurons under voltage clamp. Pflugers Arch. 1971;322(1):35–38. doi: 10.1007/BF00586662. [DOI] [PubMed] [Google Scholar]
  37. Neher E. Two fast transient current components during voltage clamp on snail neurons. J Gen Physiol. 1971 Jul;58(1):36–53. doi: 10.1085/jgp.58.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Standen N. B. Voltage-clamp studies of the calcium inward current in an identified snail neurone: comparison with the sodium inward current. J Physiol. 1975 Jul;249(2):253–268. doi: 10.1113/jphysiol.1975.sp011014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Strichartz G. R. The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol. 1973 Jul;62(1):37–57. doi: 10.1085/jgp.62.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Thompson S. H. Three pharmacologically distinct potassium channels in molluscan neurones. J Physiol. 1977 Feb;265(2):465–488. doi: 10.1113/jphysiol.1977.sp011725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tillotson D., Horn R. Inactivation without facilitation of calcium conductance in caesium-loaded neurones of Aplysia. Nature. 1978 May 25;273(5660):312–314. doi: 10.1038/273312a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES