The role of strychnine-sensitive nACHRs in rabbit retinal OFF ganglion cells
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 mediating response properties of retinal ganglion cells in rabbit retina (Linn, 1998; Protti et al., 2005). For example, application of micromolar concentrations of strychnine have revealed an ON response in OFF ganglion cells (Jensen, 1991) and this revealed ON response has been attributed to the blockade of glycinergic suppression. However, studies have shown that strychnine, in the concentrations commonly used, is also a potent competitive antagonist of alpha7 nicotinic acetylcholine receptors (nAChRs; Matsubayashi et al., 1998). Because previous studies used non-specific concentrations of strychnine to test the role of glycine in the retina, there are now questions about what role glycine and nAChRs have in mediating ganglion cell response properties. The hypothesis that micromolar concentrations of strychnine attenuate alpha7 nAChR-mediated retinal ganglion cell responses in rabbit retina was supported. The attenuation of nAChR-mediated ganglion cell responses by strychnine lead to the hypothesis that the revealed ON response in OFF ganglion cells described in Jensen’s study was actually the result of the blockade of alpha7 nAChRs rather than through blockade of glycine receptors. Application of nanomolar concentrations of strychnine did not reveal an ON response. However, application non-specific concentrations of strychnine did reveal an ON response as did application of the alpha7 semi-specific antagonist methyllycaconitine (MLA) as well as application of the gamma-aminobutyric acid (GABA) receptor antagonist picrotoxinin. The revealed ON responses in this study were present in a sub-population of transient OFF ganglion cells which had a transient OFF response as well as a sustained component with a duration that lasted longer than 300ms. A population of alpha7-containing GABAergic amacrine cells has previously been described (Dmitrieva et al., 2007) and is a likely source of inhibition of the ON response in this sub-population of OFF ganglion cells. These data help characterize the role of nAChRs in OFF ganglions responses and begin to attempt to disentangle the effects of nAChRs previously attributed to glycine receptors.