Skip to main content Accessibility help
Hostname: page-component-55597f9d44-fnprw Total loading time: 0.311 Render date: 2022-08-10T00:01:48.362Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true

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

Published online by Cambridge University Press:  28 September 2007

Department of Vision Sciences, University Alabama-Birmingham, Birmingham, Alabama
Department of Vision Sciences, University Alabama-Birmingham, Birmingham, Alabama
Department of Psychology, University Alabama-Birmingham, Birmingham, Alabama
Department of Vision Sciences, University Alabama-Birmingham, Birmingham, Alabama


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.

Research Article
© 2007 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Baldridge, W.H. (1996). Optical recordings of the effects of cholinergic ligands on neurons in the ganglion cell layer of mammalian retina. Journal of Neuroscience 16, 50605072.Google Scholar
Breitinger, H.G. & Becker, C.M. (2002). The inhibitory glycine receptor-simple views of a complicated channel. Chembiochem 3, 10421052.3.0.CO;2-7>CrossRefGoogle Scholar
Clementi, F., Fornasari, D. & Gotti, C. (2000). Neuronal nicotinic acetylcholine receptors: From structure to therapeutics. Trends in Pharmacological Sciences 21, 3537.CrossRefGoogle Scholar
Dacheux, R.F. & Raviola, E. (1986). The rod pathway in the rabbit retina: A depolarizing bipolar and amacrine cell. Journal of Neuroscience 6, 331345.Google Scholar
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.CrossRefGoogle Scholar
Demuro, A., Palma, E., Eusebi, F. & Miledi, R. (2001). Inhibition of nicotinic acetylcholine receptors by bicuculline. Neuropharmacology 41, 854861.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Erkkila, B.E., Weiss, D.S. & Wotring, V.E. (2004). Picrotoxin-mediated antagonism of alpha3beta4 and alpha7 acetylcholine receptors. Neuroreport 15, 19691973.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Grenningloh, G., Schmieden, V., Schofield, P.R., Seeburg, P.H., Siddique, T., Mohandas, T.K., Becker, C.M. & Betz, H. (1990). Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO Journal 9, 771776.Google Scholar
Grünert, U. & Wässle, H. (1993). Immunocytochemical localization of glycine receptors in the mammalian retina. The Journal of Comparative Neurology 335, 523537.CrossRefGoogle Scholar
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.Google Scholar
Han, Y., Zhang, J. & Slaughter, M.M. (1997). Partition of transient and sustained inhibitory glycinergic input to retinal ganglion cells. Journal of Neuroscience 17, 33923400.Google Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Lindstrom, J.M. (2000). The structures of neuronal nicotinic receptors. In Handbook of Experimental Pharmacology Vol. 144, eds. Clementi, F., Fornasari, D. & Gotti, C., pp. 101162. Berlin Heidelburg: Springer-Verlag.CrossRef
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.CrossRefGoogle Scholar
Lipton, S.A. (1988). Spontaneous release of acetylcholine affects the physiological nicotinic responses of rat retinal ganglion cells in culture. Journal of Neuroscience 8, 38573868.Google Scholar
Mandelzys, A., De Koninck, P. & Cooper, E. (1995). Agonist and toxin sensitivities of ACh-evoked currents on neurons expressing multiple nicotinic ACh receptor subunits. Journal of Neurophysiology 74, 12121221.Google Scholar
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.CrossRefGoogle Scholar
Masland, R.H. & Ames, A. (1976). Responses to acetylcholine of ganglion cells in an isolated mammalian retina. Journal of Neurophysiology 39, 12201235.Google Scholar
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.Google Scholar
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.Google Scholar
Matsubayashi, H., Alkondon, M., Pereira, E.F., Swanson, K.L. & Albuquerque, E.X. (1998). Strychnine: A potent competitive antagonist of alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors in rat hippocampal neurons. Journal of Pharmacology & Experimental Therapeutics 284, 904913.Google Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Pourcho, R.G. (1979). Localization of cholinergic synapses in mammalian retina with peroxidase-conjugated alpha-bungarotoxin. Vision Research 19, 287292.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Rotolo, T.C. & Dacheux, R.F. (2003). Evidence for glycine, GABAA, and GABAB receptors on rabbit OFF-alpha ganglion cells. Visual Neuroscience 20, 285296.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Schmidt, M., Humphrey, M.F. & Wässle, H. (1987). Action and localization of acetylcholine in the cat retina. Journal of Neurophysiology 58, 9971015.Google Scholar
Seguela, P., Wadiche, J., neley-Miller, K., Dani, J.A. & Patrick, J.W. (1993). Molecular cloning, functional properties, and distribution of rat brain alpha 7: A nicotinic cation channel highly permeable to calcium. Journal of Neuroscience 13, 596604.Google Scholar
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Ueno, S., Bracamontes, J., Zorumski, C., Weiss, D.S. & Steinbach, J.H. (1997). Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor. Journal of Neuroscience 17, 625634.Google Scholar
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.CrossRefGoogle Scholar
Verbitsky, M., Rothlin, C.V., Katz, E. & Elgoyhen, A.B. (2000). Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor. Neuropharmacology 39, 25152524.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

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

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

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

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

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

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *