Skip to main content
    • Aa
    • Aa

Strychnine, but not PMBA, inhibits neuronal nicotinic acetylcholine receptors expressed by rabbit retinal ganglion cells

  • J.M. RENNA (a1), C.E. STRANG (a1), F.R. AMTHOR (a2) and K.T. KEYSER (a1)

Strychnine is considered a selective competitive antagonist of glycine gated Cl channels (Saitoh et al., 1994) and studies have used strychnine at low micromolar concentrations to study the role of glycine in rabbit retina (Linn, 1998; Protti et al., 2005). However, other studies have shown that strychnine, in the concentrations commonly used, is also a potent competitive antagonist of α7 nicotinic acetylcholine receptors (nAChRs; Matsubayashi et al., 1998). We tested the effects of low micromolar concentrations of strychnine and 3-[2′-phosphonomethyl[1,1′-biphenyl]-3-yl] alanine (PMBA), a specific glycine receptor blocker (Saitoh et al., 1994; Hosie et al., 1999) on the activation of both α7 nAChRs on retinal ganglion cells and on ganglion cell responses to a light flash. Extracellular recordings were obtained from ganglion cells in an isolated retina/choroid preparation and 500 μM choline was used as an α7 agonist (Alkondon et al., 1997). We recorded from brisk sustained and brisk transient OFF cells, many of which have been previously shown to have α7 receptors (Strang et al., 2005). Further, we tested the effect of strychnine, PMBA and α-bungarotoxin on the binding of tetramethylrhodamine α-bungarotoxin in the inner plexiform layer. Our data indicates that strychnine, at doses as low as 1.0 μM, can inhibit the α7 nAChR-mediated response to choline, but PMBA at concentrations as high as 0.4 μM does not. Binding studies show strychnine and α-bungarotoxin inhibit binding of labeled α-bungarotoxin in the IPL. Thus, the effects of strychnine application may be to inhibit glycine receptors expressed by ganglion cell or to inhibit amacrine cell α7 nAChRs, both of which would result in an increase in the ganglion cell responses. Further research will be required to disentangle the effects of strychnine previously believed to be caused by a single mechanism of glycine receptor inhibition.

Corresponding author
Address Correspondence and reprint requests to: Kent T. Keyser, Director, Vision Science Research Center, Worrell Building, 924 South 18th Street, Birmingham, AL 35294. E-mail:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

Alkondon, M., Pereira, E.F., Cortes, W.S., Maelicke, A. & Albuquerque, E.X. (1997). Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons. European Journal of Neuroscience 9, 27342742.

Amthor, F.R., Keyser, K.T. & Dmitrieva, N.A. (2002). Effects of the destruction of starburst-cholinergic amacrine cells by the toxin AF64A on rabbit retinal directional selectivity. Visual Neuroscience 19, 495509.

Amthor, F.R., Takahashi, E.S. & Oyster, C.W. (1989). Morphologies of rabbit retinal ganglion cells with concentric receptive fields. Journal of Comparative Neurology 280, 7296.

Breitinger, H.G. & Becker, C.M. (2002). The inhibitory glycine receptor-simple views of a complicated channel. Chembiochem 3, 10421052.

Clementi, F., Fornasari, D. & Gotti, C. (2000). Neuronal nicotinic acetylcholine receptors: From structure to therapeutics. Trends in Pharmacological Sciences 21, 3537.

Davidoff, R.A., Aprison, M.H. & Werman, R. (1969). The effects of strychnine on the inhibition of interneurons by glycine and gamma-aminobutyric acid. International Journal of Neuropharmacology 8, 191194.

Demuro, A., Palma, E., Eusebi, F. & Miledi, R. (2001). Inhibition of nicotinic acetylcholine receptors by bicuculline. Neuropharmacology 41, 854861.

Dmitrieva, N.A., Pow, D.V., Lindstrom, J.M. & Keyser, K.T. (2003). Identification of cholinoceptive glycinergic neurons in the mammalian retina. Journal of Comparative Neurology 456, 167175.

Dmitrieva, N.A., Strang, C.E. & Keyser, K.T. (2007). Expression of alpha 7 nicotinic acetylcholine receptors by bipolar, amacrine and ganglion cells of the rabbit retina. Journal of Histochemistry & Cytochemistry 55, 461476.

Elgoyhen, A.B., Johnson, D.S., Boulter, J., Vetter, D.E. & Heinemann, S. (1994). Alpha 9: An acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell 79, 705715.

Elgoyhen, A.B., Vetter, D.E., Katz, E., Rothlin, C.V., Heinemann, S.F. & Boulter, J. (2001). alpha10: A determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells. Proceedings of the National Academy of Sciences of the United States of America 98, 35013506.

Erkkila, B.E., Weiss, D.S. & Wotring, V.E. (2004). Picrotoxin-mediated antagonism of alpha3beta4 and alpha7 acetylcholine receptors. Neuroreport 15, 19691973.

Glowatzki, E., Wild, K., Brandle, U., Fakler, G., Fakler, B., Zenner, H.P. & Ruppersberg, J.P. (1995). Cell-specific expression of the alpha 9 n-ACh receptor subunit in auditory hair cells revealed by single-cell RT-PCR. Proceedings. Biological Sciences 262, 141147.

Gotti, C., Mazzola, G., Longhi, R., Fornasari, D. & Clementi, F. (1987). The binding site for alpha-bungarotoxin resides in the sequence 188-201 of the alpha-subunit of acetylcholine receptor: Structure, conformation and binding characteristics of peptide [Lys] 188-201. Neuroscience Letters 82, 113119.

Grünert, U. & Wässle, H. (1993). Immunocytochemical localization of glycine receptors in the mammalian retina. The Journal of Comparative Neurology 335, 523537.

Grzywacz, N.M., Tootle, J.S. & Amthor, F.R. (1997). Is the input to a GABAergic or cholinergic synapse the sole asymmetry in rabbit's retinal directional selectivity? Visual Neuroscience 14, 3954.

Hosie, A.M., Akagi, H., Ishida, M. & Shinozaki, H. (1999). Actions of 3-[2'-phosphonomethyl[1,1′-biphenyl]-3-yl]alanine (PMBA) on cloned glycine receptors. British Journal of Pharmacology 126, 12301236.

Ikeda, H. & Sheardown, M.J. (1982). Acetylcholine may be an excitatory transmitter mediating visual excitation of “transient” cells with the periphery effect in the cat retina: Iontophoretic studies in vivo. Neuroscience 7, 12991308.

Jensen, R.J. (1991). Involvement of glycinergic neurons in the diminished surround activity of ganglion cells in the dark-adapted rabbit retina. Visual Neuroscience 6, 4353.

Kuhse, J., Betz, H. & Kirsch, J. (1995). The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex. Current Opinion in Neurobiology 5, 318323.

Langosch, D., Thomas, L. & Betz, H. (1988). Conserved quaternary structure of ligand-gated ion channels: The postsynaptic glycine receptor is a pentamer. Proceedings of the National Academy of Sciences of the United States of America 85, 73947398.

Linn, D.M. (1998). A comparison of the inhibitory actions of glycine and GABA on acetylcholine release from the rabbit retina. Visual Neuroscience 15, 10571065.

Marinou, M. & Tzartos, S.J. (2003). Identification of regions involved in the binding of alpha-bungarotoxin to the human alpha7 neuronal nicotinic acetylcholine receptor using synthetic peptides. The Biochemical Journal 372, 543554.

Masland, R.H., Mills, J.W. & Cassidy, C. (1984a). The functions of acetylcholine in the rabbit retina. Proceedings of the Royal Society of London—Series B: Biological Sciences 223, 121139.

Masland, R.H., Mills, J.W. & Hayden, S.A. (1984b). Acetylcholine-synthesizing amacrine cells: identification and selective staining by using radioautography and fluorescent markers. Proceedings of the Royal Society of London—Series B: Biological Sciences 223, 79100.

Nguyen, V.T., Ndoye, A. & Grando, S.A. (2000). Novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion is targeted by Pemphigus vulgaris autoimmunity. American Journal of Pathology 157, 13771391.

Peng, H., Ferris, R.L., Matthews, T., Hiel, H., Lopez-Albaitero, A. & Lustig, L.R. (2004). Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes. Life Sciences 76, 263280.

Pourcho, R.G. (1979). Localization of cholinergic synapses in mammalian retina with peroxidase-conjugated alpha-bungarotoxin. Vision Research 19, 287292.

Protti, D.A., Flores-Herr, N., Li, W., Massey, S.C. & Wässle, H. (2005). Light signaling in scotopic conditions in the rabbit, mouse and rat retina: A physiological and anatomical study. Journal of Neurophysiology 93, 34793488.

Reed, B.T., Amthor, F.R. & Keyser, K.T. (2002). Rabbit retinal ganglion cell responses mediated by alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors. Visual Neuroscience 19, 427438.

Reed, B.T., Keyser, K.T. & Amthor, F.R. (2004). MLA-sensitive cholinergic receptors involved in the detection of complex moving stimuli in retina. Visual Neuroscience 21, 861872.

Rotolo, T.C. & Dacheux, R.F. (2003). Evidence for glycine, GABAA, and GABAB receptors on rabbit OFF-alpha ganglion cells. Visual Neuroscience 20, 285296.

Saitoh, T., Ishida, M., Maruyama, M. & Shinozaki, H. (1994). A novel antagonist, phenylbenzene omega-phosphono-alpha-amino acid, for strychnine-sensitive glycine receptors in the rat spinal cord. British Journal of Pharmacology 113, 165170.

Sgard, F., Charpantier, E., Bertrand, S., Walker, N., Caput, D., Graham, D., Bertrand, D. & Besnard, F. (2002). A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit. Molecular Pharmacology 61, 150159.

Strang, C.E., Andison, M.E., Amthor, F.R. & Keyser, K.T. (2005). Rabbit retinal ganglion cells express functional α7 nAChRs. American Journal of Physiology–Cell Physiology 289, C644C655.

Vandenberg, R.J., French, C.R., Barry, P.H., Shine, J. & Schofield, P.R. (1992). Antagonism of ligand-gated ion channel receptors: two domains of the glycine receptor alpha subunit form the strychnine-binding site. Proceedings of the National Academy of Sciences of the United States of America 89, 17651769.

Verbitsky, M., Rothlin, C.V., Katz, E. & Elgoyhen, A.B. (2000). Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor. Neuropharmacology 39, 25152524.

Wehrwein, E., Hoffle, A., Thompson, S.A., Coulibaly, S.F., Linn, D.M. & Linn, C.L. (2004). Acetylcholine protects isolated adult pig retinal ganglion cells from glutamate-induced excitotoxicity. Investigative Ophthalmology & Visual Science 45, 15311543.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Visual Neuroscience
  • ISSN: 0952-5238
  • EISSN: 1469-8714
  • URL: /core/journals/visual-neuroscience
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 4
Total number of PDF views: 5 *
Loading metrics...

Abstract views

Total abstract views: 103 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 27th May 2017. This data will be updated every 24 hours.