Neural nicotinic acetylcholine responses in solitary mammalian retinal ganglion cells.
Using the patch-clamp technique, whole-cell recordings from solitary rat retinal ganglion cells in culture have established the nicotinic nature of the acetylcholine responses in these central neurons. Currents produced by acetylcholine (5-20 mumol/l) or nicotine (5-20 mumol/l) reversed in polarity near -5 mV and were unaffected by atropine (10 mumol/l). Agonist-induced currents were blocked by low doses (2-10 mumol/l) of the classical 'ganglionic' antagonists hexamethonium and mecamylamine, as well as by d-tubocurarine and dihydro-beta-erythroidine (the latter two do not discriminate clearly between ganglionic and neuromuscular junction receptors). Treatment with the potent neuromuscular blocking agent alpha-bungarotoxin (10 mumol/l) did not affect the cholinergic responses of these cells, while toxin F (0.2 mumol/l), a neural nicotinic receptor antagonist, readily abolished acetylcholine-induced currents. Thus, the experiments performed to date show that the nicotinic responses of retinal ganglion cells in the central nervous system share the pharmacology of autonomic ganglion cells in the peripheral nervous system. The ionic current carried by the nicotinic channels was selective for cations, similar to that described for nicotinic channels in other tissues. In addition, single-channel currents elicited by acetylcholine were observed in whole-cell recordings with seals greater than 5 G omega as well as in occasional outside-out patches of membrane. These acetylcholine-activated events, which had a unitary conductance of 48 pS and a reversal potential of 0 mV, represent the ion channels that mediate the neural nicotinic responses observed in these experiments on retinal ganglion cells.
Lipton
S A
SA
Division of Neuroscience, Children's Hospital, Boston, MA 02115.
Aizenman
E
E
Loring
R H
RH
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D004594:Electrophysiology; D066298:In Vitro Techniques; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D012160:Retina / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D014118:Toxins, Biological / Q000494:pharmacology
D010276:Parasympatholytics; D010277:Parasympathomimetics; D014118:Toxins, Biological; D000109:Acetylcholine