Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1987 Dec;393:331–353. doi: 10.1113/jphysiol.1987.sp016826

Outward currents of single hippocampal cells obtained from the adult guinea-pig.

R E Numann 1, W J Wadman 1, R K Wong 1
PMCID: PMC1192396  PMID: 2451740

Abstract

1. Neurones were isolated from the hippocampus of adult guinea-pigs by enzymatic and mechanical treatment. The electrophysiological properties of these cells were examined immediately after dissociation by intracellular recordings using low-resistance electrodes (2-5 M omega). 2. Pyramidal-shaped cells were identified visually. Intracellular recordings showed that these cells have input resistances ranging from 200 to 1300 M omega. Passive voltage responses to hyperpolarizing current injection were fitted by single exponentials decaying with time constants ranging from 15 to 60 ms. This suggests that the electrotonic structure of these cells is compact such that injected current elicited isopotential intracellular responses. 3. Outward currents activated by depolarization were examined in these cells using voltage-clamp techniques. The amplitude and the time course of the outward currents were profoundly affected by the holding potential. For cells held at -50 mV or more positive, depolarizing steps produced a slowly rising outward current. At holding potentials negative to -55 mV depolarizing pulses produced an additional early transient outward current followed by a slowly rising component which decayed gradually during sustained depolarizations. 4. The outward currents were separated by their kinetic properties and their sensitivity to cobalt (Co2+), tetraethylammonium (TEA) and 4-aminopyridine (4-AP). 5. The transient current peaked within 6 ms of the onset of depolarizing pulses. It decayed exponentially with a time constant of 20-40 ms. The amplitude of the current activated by a fixed depolarization increased gradually as the duration or the amplitude of the hyperpolarizing pre-pulse increased. The current activated by a fixed depolarization reached its half-maximal level when the hyperpolarizing pre-pulse was at -83 mV. 6. 4-AP exerted two actions on the transient current. Firstly, the time constant of the falling phase decreased by about a factor of two. Secondly, the current was blocked in a time- and voltage-dependent manner: the block increased when the hyperpolarizing pre-pulse lengthened. TEA, up to 10 mM, did not affect the amplitude of the transient current. Co2+ suppressed this current. The effects of Co2+ consisted of a shift to the positive direction of the voltage dependence of the current. 7. The delayed currents can be divided into Ca2+-dependent and Ca2+-independent components. The component persistent in the Co2+ solution (K-current) decayed slowly with maintained depolarization (time constant greater than 3 s).(ABSTRACT TRUNCATED AT 400 WORDS)

Full text

PDF
331

Images in this article

Selected References

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

  1. Alger B. E., Nicoll R. A. Epileptiform burst afterhyperolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science. 1980 Dec 5;210(4474):1122–1124. doi: 10.1126/science.7444438. [DOI] [PubMed] [Google Scholar]
  2. Brown D. A., Griffith W. H. Calcium-activated outward current in voltage-clamped hippocampal neurones of the guinea-pig. J Physiol. 1983 Apr;337:287–301. doi: 10.1113/jphysiol.1983.sp014624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown D. A., Griffith W. H. Persistent slow inward calcium current in voltage-clamped hippocampal neurones of the guinea-pig. J Physiol. 1983 Apr;337:303–320. doi: 10.1113/jphysiol.1983.sp014625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. FRANKENHAEUSER B. The effect of calcium on the myelinated nerve fibre. J Physiol. 1957 Jul 11;137(2):245–260. doi: 10.1113/jphysiol.1957.sp005809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gorman A. L., Thomas M. V. Potassium conductance and internal calcium accumulation in a molluscan neurone. J Physiol. 1980 Nov;308:287–313. doi: 10.1113/jphysiol.1980.sp013472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gustafsson B., Galvan M., Grafe P., Wigström H. A transient outward current in a mammalian central neurone blocked by 4-aminopyridine. Nature. 1982 Sep 16;299(5880):252–254. doi: 10.1038/299252a0. [DOI] [PubMed] [Google Scholar]
  8. Haas H. L., Konnerth A. Histamine and noradrenaline decrease calcium-activated potassium conductance in hippocampal pyramidal cells. 1983 Mar 31-Apr 6Nature. 302(5907):432–434. doi: 10.1038/302432a0. [DOI] [PubMed] [Google Scholar]
  9. Halliwell J. V., Adams P. R. Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 1982 Oct 28;250(1):71–92. doi: 10.1016/0006-8993(82)90954-4. [DOI] [PubMed] [Google Scholar]
  10. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  11. Hotson J. R., Prince D. A., Schwartzkroin P. A. Anomalous inward rectification in hippocampal neurons. J Neurophysiol. 1979 May;42(3):889–895. doi: 10.1152/jn.1979.42.3.889. [DOI] [PubMed] [Google Scholar]
  12. Johnston D., Hablitz J. J., Wilson W. A. Voltage clamp discloses slow inward current in hippocampal burst-firing neurones. Nature. 1980 Jul 24;286(5771):391–393. doi: 10.1038/286391a0. [DOI] [PubMed] [Google Scholar]
  13. KANDEL E. R., SPENCER W. A. Electrophysiology of hippocampal neurons. II. After-potentials and repetitive firing. J Neurophysiol. 1961 May;24:243–259. doi: 10.1152/jn.1961.24.3.243. [DOI] [PubMed] [Google Scholar]
  14. Kay A. R., Wong R. K. Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus. J Physiol. 1987 Nov;392:603–616. doi: 10.1113/jphysiol.1987.sp016799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kay A. R., Wong R. K. Isolation of neurons suitable for patch-clamping from adult mammalian central nervous systems. J Neurosci Methods. 1986 May;16(3):227–238. doi: 10.1016/0165-0270(86)90040-3. [DOI] [PubMed] [Google Scholar]
  16. Lancaster B., Adams P. R. Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons. J Neurophysiol. 1986 Jun;55(6):1268–1282. doi: 10.1152/jn.1986.55.6.1268. [DOI] [PubMed] [Google Scholar]
  17. Madison D. V., Nicoll R. A. Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro. J Physiol. 1984 Sep;354:319–331. doi: 10.1113/jphysiol.1984.sp015378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Madison D. V., Nicoll R. A. Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus. Nature. 1982 Oct 14;299(5884):636–638. doi: 10.1038/299636a0. [DOI] [PubMed] [Google Scholar]
  19. Miles R., Wong R. K. Excitatory synaptic interactions between CA3 neurones in the guinea-pig hippocampus. J Physiol. 1986 Apr;373:397–418. doi: 10.1113/jphysiol.1986.sp016055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miles R., Wong R. K. Single neurones can initiate synchronized population discharge in the hippocampus. Nature. 1983 Nov 24;306(5941):371–373. doi: 10.1038/306371a0. [DOI] [PubMed] [Google Scholar]
  21. Nakajima Y., Nakajima S., Leonard R. J., Yamaguchi K. Acetylcholine raises excitability by inhibiting the fast transient potassium current in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 1986 May;83(9):3022–3026. doi: 10.1073/pnas.83.9.3022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Neher E., Lux H. D. Differential action of TEA + on two K + -current componentss of a molluscan neurone. Pflugers Arch. 1972;336(2):87–100. doi: 10.1007/BF00592924. [DOI] [PubMed] [Google Scholar]
  23. Pennefather P., Lancaster B., Adams P. R., Nicoll R. A. Two distinct Ca-dependent K currents in bullfrog sympathetic ganglion cells. Proc Natl Acad Sci U S A. 1985 May;82(9):3040–3044. doi: 10.1073/pnas.82.9.3040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schwartzkroin P. A. Further characteristics of hippocampal CA1 cells in vitro. Brain Res. 1977 Jun 3;128(1):53–68. doi: 10.1016/0006-8993(77)90235-9. [DOI] [PubMed] [Google Scholar]
  25. Schwartzkroin P. A., Stafstrom C. E. Effects of EGTA on the calcium-activated afterhyperpolarization in hippocampal CA3 pyramidal cells. Science. 1980 Dec 5;210(4474):1125–1126. doi: 10.1126/science.6777871. [DOI] [PubMed] [Google Scholar]
  26. Schwindt P. C., Crill W. E. Differential effects of TEA and cations on outward ionic currents of cat motoneurons. J Neurophysiol. 1981 Jul;46(1):1–16. doi: 10.1152/jn.1981.46.1.1. [DOI] [PubMed] [Google Scholar]
  27. Segal M., Barker J. L. Rat hippocampal neurons in culture: potassium conductances. J Neurophysiol. 1984 Jun;51(6):1409–1433. doi: 10.1152/jn.1984.51.6.1409. [DOI] [PubMed] [Google Scholar]
  28. Segal M., Rogawski M. A., Barker J. L. A transient potassium conductance regulates the excitability of cultured hippocampal and spinal neurons. J Neurosci. 1984 Feb;4(2):604–609. doi: 10.1523/JNEUROSCI.04-02-00604.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Thompson S. Aminopyridine block of transient potassium current. J Gen Physiol. 1982 Jul;80(1):1–18. doi: 10.1085/jgp.80.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Traub R. D. Simulation of intrinsic bursting in CA3 hippocampal neurons. Neuroscience. 1982 May;7(5):1233–1242. doi: 10.1016/0306-4522(82)91130-7. [DOI] [PubMed] [Google Scholar]
  32. Traub R. D., Wong R. K. Cellular mechanism of neuronal synchronization in epilepsy. Science. 1982 May 14;216(4547):745–747. doi: 10.1126/science.7079735. [DOI] [PubMed] [Google Scholar]
  33. Wong R. K., Prince D. A. Afterpotential generation in hippocampal pyramidal cells. J Neurophysiol. 1981 Jan;45(1):86–97. doi: 10.1152/jn.1981.45.1.86. [DOI] [PubMed] [Google Scholar]
  34. Wong R. K., Prince D. A. Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res. 1978 Dec 29;159(2):385–390. doi: 10.1016/0006-8993(78)90544-9. [DOI] [PubMed] [Google Scholar]
  35. Zbicz K. L., Weight F. F. Transient voltage and calcium-dependent outward currents in hippocampal CA3 pyramidal neurons. J Neurophysiol. 1985 Apr;53(4):1038–1058. doi: 10.1152/jn.1985.53.4.1038. [DOI] [PubMed] [Google Scholar]

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

RESOURCES