Skip to main content
Log in

Different Effects of 5-HT1 and 5-HT2 Receptor Agonists on Excitability Modulation of Motoneurons in Frog Spinal Cord

  • Comparative and Ontogenic Biochemistry
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

Effects of 5-HT1 and 5-HT2 receptor agonists and antagonists on membrane properties of motoneurons in the isolated lumbar segment of the frog spinal cord were investigated using intracellular recordings. Application of a 5-HT2A,B,C receptor agonist α-Me-5-HT evoked depolarization of the motoneuronal membrane. The co-application of α-Me-5-HT and a specific 5-HT2B receptor antagonist SB 206553 did not result in depolarization. α-Me-5-HT reduced the amplitude of medium afterhyperpolarization and increased the number of antidromic action potentials (APs). The application of an antagonist SB 206553 abolished these effects. A 5-HT1A/7 receptor agonist 8-OH-DPAT had a time-dependent effect on the number of antidromic APs, evoking an initial short-term excitation followed by an inhibition. The data obtained in our experiments indicate the presence of 5-HT1A/7 and 5-HT2B,C receptors on the postsynaptic membrane of motoneurons. We suggest a possible co-modulation of the accommodative properties of motoneurons by the two types of serotonin receptors, 5-HT2B,C and 5-HT1A.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

RMP:

resting membrane potential

AP:

action potential

5-HT:

serotonin

fAHP:

fast afterhyperpolarization

mAHP:

medium afterhyperpolarization

α-Me-5-HT (α-Methyl-5-hydroxytryptamine maleate):

specific agonist of 5-HT2A,2B,2C-receptors

8-OH-DPAT(±)-(8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide):

agonist of 5-HT1A/7-receptors

sumatriptan (3-[2-(Dimethylamino) ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate):

agonist of 5-HT 1B/D-receptors

ketanserin (3-[2-[4-(4-Fluorobenzoyl)-1-piperidinyl]ethyl]-2,4[1H,3H]-quinazolinedione tartrate):

selective antagonist of 5-HT2A-receptors

SB 206553 (3,5-Dihydro-5-methyl-N-3-pyridinylbenzo[1,2-b:4,5-b’]dipyrrole-1(2H)-carboxamide hydrochloride:

selective antagonist of 5-HT2B,2C-receptors

References

  1. Nakamura, K. and Wong-Lin, K., Functions and computational principles of serotonergic and related systems at multiple scales, Front. Integr. Neurosci., 2014, vol. 8, pp. 1–2.

    Google Scholar 

  2. Ghosh, M. and Pearse, D., The role of the serotonergic system in locomotor recovery after spinal cord injury, Front. Neural Circuits, article 151, 2015, vol. 8, pp. 1–14. doi: https://doi.org/10.3389/fncir.2014.00151

    Article  CAS  Google Scholar 

  3. Perrier, J.-F., Rasmussen, H.B., Christensen, R.K., and Petersen, A.V., Modulation of the intrinsic properties of motoneurons by serotonin, Curr. Pharmaceut. Design, 2013, vol. 19, pp. 4371–4384.

    Article  CAS  Google Scholar 

  4. Jacobs, B.L. and Fornal, C.A., 5-HT and motor control: a hypothesis, Trends Neurosci., 1993, vol. 16, pp. 346–352.

    Article  CAS  Google Scholar 

  5. Wallis, D.I., 5-HT receptors involved in initiation or modulation of motor patterns: opportunities for drug development, Trends Pharmacol. Sci., 1994, vol. 15, pp. 288–292.

    Article  CAS  Google Scholar 

  6. Takahashi, T. and Berger, A.J., Direct excitation of rat spinal motoneurones by serotonin, J. Physiol. (Lond.), 1990, vol. 423, pp. 63–76.

    Article  CAS  Google Scholar 

  7. Garraway, S.M. and Hochman, S., Modulatory actions of serotonin, norepinephrine, dopamine, and acetylcholine in spinal cord deep dorsal horn neurons, J. Neurophysiol., 2001, vol. 86, pp. 2183–2194.

    Article  CAS  Google Scholar 

  8. Ciranna, L., Serotonin as a modulator of glutamate- and GABAmediated neurotransmission: implications in physiological functions and in pathology, Curr. Neuropharmacol., 2006, vol. 4, pp. 101–114.

    Article  CAS  Google Scholar 

  9. Fink, K.B. and Gőthert, M., 5-HT receptor regulation of neurotransmitter release, Pharmacol. Rev., 2007, vol. 59, pp. 360–417.

    Article  CAS  Google Scholar 

  10. Hannon, J. and Hoyer, D., Molecular biology of 5-HT receptors, Behav. Brain Res., 2008, vol. 195, pp. 198–213.

    Article  CAS  Google Scholar 

  11. El Manira, A., Zhang, W., Svensson, E., and Bussieres, N.K., 5-HT inhibits calcium current and synaptic transmission from sensory neurons in lamprey, J. Neurosci., 1997, vol. 17, pp. 1786–1794.

    Article  CAS  Google Scholar 

  12. Sillar, K.T. and Simmers, A.J., Presynaptic inhibition of primary afferent transmitter release by 5-hydroxytryptamine at a mechanosensory synapse in the vertebrate spinal cord, J. Neurosci., 1994, vol. 74, pp. 2636–2647.

    Article  Google Scholar 

  13. Holohean, A.M., Hackman, J.C., and Davidoff, R.A., Changes in membrane potential of frog motoneurons induced by activation of serotonin receptor subtypes, Neurosci., 1990, vol. 34, pp. 555–564.

    Article  CAS  Google Scholar 

  14. Holohean, A.M., Hackman, J.C., Shope, S.B., and Davidoff, R.A., Activation of 5-HT1C/2 receptors depresses polysynaptic reflexes and excitatory amino acid-induced motoneuron responses in frog spinal cord, Brain Res., 1992, vol. 579, pp. 8–16.

    Article  CAS  Google Scholar 

  15. Holohean, A.M. and Hackman, J.C., Mechanisms intrinsic to 5-HT2B receptor-induced potentiation of NMDA receptor responses in frog motoneurones, Br. J. Pharmacol., 2004, vol. 143 (3), pp. 351–360.

    Article  CAS  Google Scholar 

  16. Ovsepian, S.V. and Vesselkin, N.P., Serotonergic modulation of synaptic transmission and action potential firing in frog motoneurons, Brain Res., 2006, vol. 1102, pp. 71–77. doi: https://doi.org/10.1016/j.brainres.2006.04.035

    Article  CAS  Google Scholar 

  17. Kalinina, N.I., Kurchavyi, G.G., Zaitsev, A.V., and Veselkin, N.P., Presynaptic serotonergic modulation of spontaneous and miniature synaptic activity in frog lumbar motoneurons, J. Evol. Biochem. Physiol., 2016, vol. 52 (5), pp. 359–368.

    Article  CAS  Google Scholar 

  18. Kalinina, N.I., Zaitsev, A.V., and Vesselkin, N.P., Presynaptic serotonin 5-HT1B/D receptor mediated inhibition of glycinergic transmission to the frog spinal motoneurons, J. Comp. Physiol. A, 2018, vol. 204 (3), pp. 329–337. doi: https://doi.org/10.1007/s00359-017-1244-y

    Article  CAS  Google Scholar 

  19. Bayliss, D.A., Umemiya, M., and Berger, A.J., Inhibition of N- and P-type calcium currents and the after-hyperpolarization in rat motoneurones by serotonin, J. Physiol., 1995, vol. 485, pp. 635–647.

    Article  CAS  Google Scholar 

  20. Hsiao, C.F., Trueblood, P.R., Levine, M.S., and Chan, S.H., Multiple effects of serotonin on membrane properties of trigeminal motoneurons in vitro, J. Neurophysiol., 1997, vol. 77, pp. 2910–2924.

    Article  CAS  Google Scholar 

  21. Wallen, P., Buchanan, J.T., Grillner, S., Hill, R.H., Christenson, J., and Hokfelt, T., Effects of 5-hydroxytryptamine on the afterhyperpolarization, spike frequency regulation, and oscillatory membrane properties in lamprey spinal cord neurons, J. Neurophysiol., 1989, vol. 61, pp. 759–768.

    Article  CAS  Google Scholar 

  22. Meer, D.P. and Buchanan, J.T., Apamin reduces the late afterhyperpolarization of lamprey spinal neurons, with little effect on fictive swimming, Neurosci. Lett., 1992, vol. 143, pp. 1–4.

    Article  CAS  Google Scholar 

  23. Miles, G.B. and Sillar, K.T., Neuromodulation of vertebrate locomotor control networks, Physiol., 2011, vol. 26, pp. 393–441. doi: https://doi.org/10.1152/physiol.00013.2011

    Article  CAS  Google Scholar 

  24. Grunnet, M., Jespersen, T., and Perrier, J.-F., 5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels, J. Neurosci. Res., 2004, vol. 78, pp. 845–854. https://doi.org/10.1002/jnr.20318

    Article  CAS  Google Scholar 

  25. Wikstrom, M., Hill, R., Hellgren, J., and Grillner, S., The action of 5-HT on calcium-dependent potassium channels and on the spinal locomotor network in lamprey is mediated by 5-HT1A like receptors, Brain Res., 1995, vol. 678 (1–2), pp. 191–199. doi: 0006-8993(95)00183-Q

    Article  CAS  Google Scholar 

  26. Harvey, P.J., Li, X., Li, Y., and Bennett, D.J., 5-HT2 receptor activation facilitates a persistent sodium current and repetitive firing in spinal motoneurons of rats with and without chronic spinal cord injury. J. Neurophysiol., 2006, vol. 96 (3), pp. 1158–1170. doi: https://doi.org/10.1152/jn.01088.2005

    Article  CAS  Google Scholar 

  27. Murray, K.C., Stephens, M.J., Ballou, E.W, Heckman, C.J., and Bennett, D.J., Motoneuron excitability and muscle spasms are regulated by 5-HT2B and 5-HT2C receptor activity, J. Neurophysiol., 2011, vol. 105, pp. 731–748.

    Article  Google Scholar 

  28. Perrier, J.F. and Hounsgaard, J., 5-HT2 receptors promote plateau potentials in turtle spinal motoneurons by facilitating a L-type calcium current, J. Neurophysiol., 2003, vol. 89, pp. 954–959.

    Article  CAS  Google Scholar 

  29. Sah, P., Ca2+-activated K+ currents in neurones: types, physiological roles and modulation, TINS, 1996, vol. 19 (4), pp. 150–154. https://doi.org/10.1016/S0166-2236(96)80026-9

    CAS  PubMed  Google Scholar 

  30. Li, X. and Bennett, D.J., Apamin-sensitive calcium-activated potassium currents (SK) are activated by persistent calcium currents in rat motoneurons, J. Neurophysiol., 2007, vol. 97, pp. 3314–3330.

    Article  CAS  Google Scholar 

  31. Inoue, T., Itoh, S., Kobayashi, M., Kang, Y., Matsuo, R., Wakisaka, S., and Morimoto, T., Serotonergic modulation of the hyperpolarizing spike afterpotential in rat jaw-closing motoneurons by PKA and PKC, J. Neurophysiol., 1999, vol. 82, pp. 626–637.

    Article  CAS  Google Scholar 

  32. Perrier, J.F. and Delgado-Lezama, R., Synaptic release of serotonin induced by stimulation of the raphe nucleus promotes plateau potentials in spinal motoneurons of the adult turtle, J. Neurosci., 2005, vol. 25, pp. 7993–7999.

    Article  CAS  Google Scholar 

  33. Husch, A., Van Patten, G.N., Hong, D.N., Scaperotti, M.M., Cramer, N., and Harris-Warrick, R.M., Spinal cord injury induces serotonin supersensitivity without increasing intrinsic excitability of mouse V2a interneurons, J. Neurosci., 2012, vol. 32, pp. 13 145–13 154.

    Article  CAS  Google Scholar 

  34. Cotel, F., Exley, R., Cragg, S.J., and Perrier, J.-F., Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation, PNAS Early Edition, 2013, vol. 1–6. https://doi.org/10.1073/pnas.1216150110

    Article  CAS  Google Scholar 

  35. Hochman, S., Garraway, S.M., Machacek, D.W., and Shay, B.L., 5-HT receptors and the neuromodulatory control of spinal cord function, Motor Neurobiology of the Spinal Cord, Cope, T.C., Ed., CRC Press, 2001, pp. 47–87. doi: https://doi.org/10.1201/9781420042641.ch3

    Chapter  Google Scholar 

Download references

Funding

This study was implemented under the state assignment (reg. no. AAAA-A18-118012290372-0). Pharmacological studies were supported by the Russian Foundation for Basic Research (grant no. 18-04-00247).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. A. Kalinina.

Ethics declarations

All applicable international, national and institutional principles of handling and using experimental animals for scientific purposes were observed.

This study did not involve human subjects as research objects.

Additional information

Russian Text © The Author(s), 2019, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2019, Vol. 55, No. 4, pp. 255–262.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kalinina, N.A., Zaitsev, A.V. & Vesselkin, N.P. Different Effects of 5-HT1 and 5-HT2 Receptor Agonists on Excitability Modulation of Motoneurons in Frog Spinal Cord. J Evol Biochem Phys 55, 284–292 (2019). https://doi.org/10.1134/S0022093019040045

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093019040045

Keywords

Navigation