Strychnine, but not PMBA, inhibits neuronal nicotinic acetylcholine receptors expressed by rabbit retinal 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 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 alpha7 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 alpha7 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 microM choline was used as an alpha7 agonist (Alkondon et al., 1997). We recorded from brisk sustained and brisk transient OFF cells, many of which have been previously shown to have alpha7 receptors (Strang et al., 2005). Further, we tested the effect of strychnine, PMBA and alpha-bungarotoxin on the binding of tetramethylrhodamine alpha-bungarotoxin in the inner plexiform layer. Our data indicates that strychnine, at doses as low as 1.0 microM, can inhibit the alpha7 nAChR-mediated response to choline, but PMBA at concentrations as high as 0.4 microM does not. Binding studies show strychnine and alpha-bungarotoxin inhibit binding of labeled alpha-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 alpha7 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.
Renna
J M
JM
Department of Vision Sciences, University Alabama-Birmingham, Birmingham, Alabama 35294, USA.
Strang
C E
CE
Amthor
F R
FR
Keyser
K T
KT
D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004594:Electrophysiology; D018684:Glycine Agents / Q000494:pharmacology*; D008969:Molecular Sequence Data; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists; D063065:Organophosphonates / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010775:Photic Stimulation; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects
C091378:3-(2'-phosphonomethyl(1,1'-biphenyl)-3-yl)alanine; D002038:Bungarotoxins; D018684:Glycine Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D063065:Organophosphonates; D011978:Receptors, Nicotinic; D003035:Cobalt; D010649:Phenylalanine; D013331:Strychnine; D002794:Choline