Optical recordings of the effects of cholinergic ligands on neurons in the ganglion cell layer of mammalian retina.
Cholinergic regulation of the activity of rabbit retinal ganglion cells and displaced amacrine cells was investigated using optical recording of changes in intracellular free calcium ([Ca2+]i). Labeling of neurons in the mature retina was achieved by injecting calcium green-1 dextran (CaGD) into the isolated retina. Nicotine increased ganglion cell [Ca2+]i, affecting every loaded cell in some preparations; the pharmacology of nicotine was consistent with an action at neuronal nicotinic receptors, and specifically it was kappa-(neuronal-)bungarotoxin-sensitive but alpha-bungarotoxin-insensitive. Muscarine also raised [Ca2+]i, but it was less potent than nicotine, affecting only a subpopulation of ganglion cells, with an M1-like muscarinic receptor pharmacology. Neither the nicotine- nor muscarine-induced increases of ganglion cell [Ca2+]i were blocked by the glutamate receptor antagonists 6,7-dinitroquinoxaline-2,3-dione and aminophosphonopentanoic acid. Therefore, the effects of cholinergic agonists on ganglion cell [Ca2+]i were not attributable to an indirect effect mediated by glutamatergic bipolar cells. The effects of nicotine and muscarine were abolished in calcium-free solution, indicating that the responses depend on calcium influx. Displaced (Cb) cholinergic amacrine cells were also loaded with CaGD and were identified by selective labeling with the nuclear dye 4',6-diamidino-2-phenyl-indole. Cb amacrine cells did not respond to either nicotine or muscarine, but responded vigorously to the glutamate receptor agonist kainic acid. There is anatomical evidence indicating that cholinergic amacrine cells make synaptic contact with each other, but the present results do not support the hypothesis that communication between these cells is cholinergic.
Baldridge
W H
WH
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005260:Female; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009116:Muscarine / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D055095:Optics and Photonics; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000502:physiology; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism
D018679:Cholinergic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D009116:Muscarine; D002118:Calcium