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J.M. Renna, C.E. Strang, F.R. Amthor, K.T. Keyser; Low–Dose Strychnine and Its Effects on 7 Nicotinic Receptor Function . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2244.
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Purpose:Strychnine has been considered to be a selective competitive antagonist of glycine gated Cl– channels (Saitoh et al, 1994). Previous studies have used strychnine at low micromolar concentrations to study the role of glycine in rabbit retina. However, more recent 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 concentrations of strychnine on the activation of α7 nAChRs on retinal ganglion cells (GCs). Methods: Extracellular recordings were obtained from GCs in a rabbit eyecup preparation. After the cell was physiologically characterized, 2 mM cobalt was added to the recording medium to synaptically isolate the GC. Each cell’s response to puff application of 500 µM choline was then recorded. Subsequent trials included bath–applied strychnine at concentrations of 0.1 µM, 0.5 µM, 1.0 µM and 2.0 µM. Data were analyzed using the Wilcoxon Matched–Pairs Signed–Ranks Test with the Bonferroni correction for multiple comparisons. Results: We have concentrated mostly on OFF cells, many classes of which have been previously shown to have α7 receptors as evidenced by responses to choline under synaptic block (Strang et al., 2003). We have recorded both brisk sustained and brisk transient OFF cells. Preliminary data indicates that strychnine, at doses as low as 0.1 µM, can inhibit the response to choline by a subset of sustained OFF cells. For other cells, 2.0 µM strychnine was needed to affect the choline response. Conclusions: Choline, at 500 µM, is a subtype specific α7 nAChR agonist (Alkondon et al., 1997). Responses to choline under cobalt blockade are an indicator of α7 nAChR expression by ganglion cells. Previous studies that relied on strychnine to characterize the functions of the glycine gated Cl– channels may be compromised since α7 nAChRs may also have been inhibited at the concentrations used.
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