Calcium Influx is Responsible for Afterdepolarizations in Rat Hippocampal Dentate Granule Cells

  • Park, Won-Sun (Department of Physiology and National Research Laboratory for Cellular Signalling, Seoul National University College of Medicine) ;
  • Lee, Suk-Ho (Department of Physiology and National Research Laboratory for Cellular Signalling, Seoul National University College of Medicine)
  • Published : 2002.06.21

Abstract

Granule cells in dentate gyrus of hippocampus relay information from entorhinal cortex via perforant fiber to pyramidal cells in CA3 region. Their electrical activities are known to be closely associated with seizure activity as well as memory acquisition. Since action potential is a stereotypic phenomena which is based on all-or-none principle of $Na^+$ current, the neuronal firing pattern is mostly dependent on afterpotentials which follows the stereotypic $Na^+$ spike. Granule cells in dentate gyrus show afterdepolarization (ADP), while interneurons in dentate gyrus have afterhyperpolarizaton. In the present study, we investigated the ionic mechanism of afterdepolarization in hippocampal dentate granule cell. Action potential of dentate granule cells showed afterdepolarization, which was characterized by a sharp notch followed by a depolarizing hump starting at about $-49.04{\pm}1.69\;mV\;(n=43,\;mean{\pm}SD)$ and lasting $3{\sim}7$ ms. Increase of extracellular $Ca^{2+}$ from 2 mM to 10 mM significantly enhanced the ADP both in amplitude and in duration. A $K^+$ channel blocker, 4-aminopyridine (4-AP, 2 mM), enhanced the ADP and often induced burst firings. These effects of 10 mM $Ca^{2+}$ and 4-AP were additive. On the contrary, the ADP was significantly suppressed by removal of external $Ca^{2+},$ even in the presence of 4-AP (2 mM). A $Na^+$ channel blocker, TTX (100 nM), did not affect the ADP. From these results, it is concluded that the extracellular $Ca^{2+}$ influx contributes to the generation of ADP in granule cells.

Keywords

References

  1. Alkon DL, Amaral DG, Bear MF, Black TJ, Cohen NJ, Disterhoft JF, Eichenbaum H, Golski S, Gorman LK, et al. Learning and memory. Brain Research Reviews 16(2): 193-220, 1991 https://doi.org/10.1016/0165-0173(91)90005-S
  2. Azouz R, Jenson MS, Yarri Y. Ionic basis of spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells. J Physiol 492.1: 211-223, 1996
  3. Blaxter TJ, Carlen PL, Niesen C. Pharmacological and anatomical separation of calcium currents in rat dentate granule neurons in vitro. J Physiol 412: 93-112, 1989 https://doi.org/10.1113/jphysiol.1989.sp017605
  4. Crunelli V, Assaf SY, Kelly JS. Intracellular recordings from granule cells of the dentate gyrus in vitro. In Neurobiology of the Hippocampus. Edited by Seifert W. New York, Academic, p 197-214, 1983
  5. Eliot LS, Johnston D. Multiple components of calcium current in acutely dissociated dentate gyrus granule neurons. J Neurophysiol 72(2): 762-777, 1994 https://doi.org/10.1152/jn.1994.72.2.762
  6. Freund TF, Buzsaki G. Interneuron of the hippocampus. Hippocampus 6: 347-470, 1996 https://doi.org/10.1002/(SICI)1098-1063(1996)6:4<347::AID-HIPO1>3.0.CO;2-I
  7. Hasuo H, Gallagher JP. Facilitatory action of muscarine on the slow afterdepolarization of rat dorsolateral septal nucleus neurons in vitro. Neuroscience Letters 112: 234-238, 1990 https://doi.org/10.1016/0304-3940(90)90209-R
  8. Hoffman DA, Jeffrey CM, Costa MC, Johnston D. $K^+$ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature 387: 869-875, 1997 https://doi.org/10.1038/43119
  9. Ildik A, William RH. Role of multiple calcium and calcium- dependent conductances in regulation of hippocampal dentate granule cell excitability. J Computational Neuroscience 6: 215-235, 1999 https://doi.org/10.1023/A:1008801821784
  10. Jensen MS, Azouz R, Yaari Y. Spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells. J Physiol 492(1): 199-210, 1996 https://doi.org/10.1113/jphysiol.1996.sp021301
  11. Jung HY, Staff NP, Spruston N. Action potential bursting in subicular pyramidal neurons in driven by a calcium tail current. J Neuroscience 21(10): 3312-3321, 2001
  12. Lee JH, Gomora JC, Cribbs LL, Perez-Reyes E. Nickel block of three cloned T-type calcium channels: low concentrations selectively block alpha1H. Biophysical J 77(6): 3034-3042, 1999 https://doi.org/10.1016/S0006-3495(99)77134-1
  13. Lopes DA, Silva FH, Witter MP, Boeijinga PH, Lothman AHM. Anatomic organization and physiology of the limbic cortex. Physiological Reviews 70: 453-511, 1990
  14. Magee JC, Carruth M. Dendritic voltage-gated ion channels regulate the action potential firing mode of hippocampal CA1 pyramidal neurons. J Neurophysiol 82(4): 1895-1901, 1999 https://doi.org/10.1152/jn.1999.82.4.1895
  15. Nissen C, Charlton MP, Carlen PL. Postsynaptic and presynaptic effects of the calcium chelator BAPTA on synaptic transmission in rat hippocampal dentate granule neurons. Brain Research 555: 319-325, 1991 https://doi.org/10.1016/0006-8993(91)90358-3
  16. Storm JF. Potassium currents in hippocampal pyramidal cells. Progress in Brain Research 83: 161-187, 1990
  17. Stuart G, Schiller J, Sakmann B. Action potential initiation and propagation in rat neocortical pyramidal neurons. J Physiol 505.3: 617-632, 1997
  18. Sugita S, Tanaka E, North RA. Membrane properties and synaptic potentials of three types of neuron in rat lateral amygdala. J Physiol 460: 705-718, 1993 https://doi.org/10.1113/jphysiol.1993.sp019495
  19. Williams SR, Stuart GJ. Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons. J Physiol 521.2: 467-482, 1999
  20. Witter MP, Groenewegen HJ, Lopes Da Silva FH, Lothman AHM. Functional organization of the extrinsic and intrinsic circuitry of the hippocampal region. Progress in Neurobiol 33: 161-253, 1989 https://doi.org/10.1016/0301-0082(89)90009-9
  21. Wong RK, Prince DA. Afterpotential generation in hippocampal pyramidal cells. J Neurophysiol 45(1): 86-97, 1981 https://doi.org/10.1152/jn.1981.45.1.86
  22. Zhang L, Valiante TA, Carlen PL. Contribution of the low-threshold T-type calcium current in generating the post-spike depolarizing afterpotential in dentate granule neurons of immature rats. J Neurophysiol 70(1): 223-231, 1993 https://doi.org/10.1152/jn.1993.70.1.223