Abstract
Purpose: :
Acetylcholine (ACh) can contribute to the modulation of retinal ganglion cell (GC) response properties through either muscarinic or nicotinic acetylcholine receptor (AChR) activation (Schmidt et al., 1987; Baldridge, 1996). The cholinergic system can exert its effects via direct binding of ACh or by the binding of choline, the product of ACh hydrolysis, to subtypes of both AChRs. This study was undertaken to assess the distribution of mAChRs in relation to nAChRs in rabbit retina, and to assess the functional significance of the cholinergic system in shaping the response properties of retinal GCs through these two distinct receptor–mediated mechanisms.
Methods: :
RT–PCR was used to detect transcripts for mAChR subtypes in rabbit retina. For immunohistochemical studies, antibodies against mAChRs and nAChRs were used. Extracellular recordings were used to assess GC responses to application of AChR agonists and antagonists. Choline was used as an agonist. Atropine and hexamethonium bromide (HMB) were used as mAChR and nAChR antagonists, respectively.
Results: :
Rabbit transcripts for M1–M5 mAChRs were 83–95% homologous to human mAChRs. Single and double labeling studies demonstrated that M2 and M4 AChRs were expressed by amacrine cells, including cholinergic amacrine cells, and subsets of GCs. M3 receptors were expressed by horizontal cells and a population of bipolar cells. mAChR expression overlapped, but was not identical to, that of nAChRs. To assess the functional significance the distribution of AChRs, GC responses to agonist puffs were tested. Choline application could either enhance or suppress GC responses. These effects could be reduced by application of mAChR and/or nAChR antagonists. When tested together mAChR and nAChR antagonists exerted opposite effects.
Conclusions: :
mAChR activation can affect K+ and Ca2+ conductance. In general, the activation of M3 mAChRs decreases K+ conductances while M2 and M4 activation can increase K+ conductances (Brown et al., 1997). The differential distribution of mAChRs and nAChRs and opposing effects of antagonists allow for the possibility that there is a push–pull interaction between nicotinic and muscarinic effects.
Keywords: acetylcholine • ganglion cells • neurotransmitters/neurotransmitter systems