Acetylcholine-induced electrical responses in neuroblastoma cells.
The response to iontophoretic application of acetylcholine in the mouse neuroblastoma cell line N1E-115 was composed of three phases. The initial fast depolarizing phase was blocked by 10 microM d-tubocurarine, but not by 0.1 microM atropine. This phase was followed by a transient hyperpolarization which in turn was followed by a secondary slow depolarization. Both the hyperpolarization and slow depolarization were blocked by atropine (0.1 microM), but not by d-tubocurarine (10 microM). The hyperpolarization and slow depolarization were also evoked by iontophoretic application of the muscarinic agonist methacholine. Under voltage-clamp conditions, an initial fast inward current, a transient outward current, and a secondary slow inward current were recorded in response to acetylcholine application. These three phases of current correspond to the three phases of the membrane potential response. The initial fast inward current increased in amplitude by hyperpolarization of the membrane, and decreased by depolarization. The mean reversal potential was estimated to be -1 mV. The outward current increased in amplitude by depolarization, decreased by hyperpolarization, and reversed its polarity at -67 mV. Alteration of external K+ concentration shifted the reversal potential in the manner expected for an increase in potassium permeability. The slow inward current increased in amplitude by hyperpolarization, decreased by depolarization, and reversed its polarity at +20 mV. It is concluded that the initial fast inward current is mediated by a nicotinic receptor similar to that in muscle end-plate membranes and in postsynaptic membranes of the sympathetic ganglia. Both the outward current and the slow inward current are mediated by muscarinic receptors. The outward current results from an increase in the membrane permeability to K+, and the slow current appears to be carried, at least in part, by Na+.
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004553:Electric Conductivity; D004594:Electrophysiology; D007478:Iontophoresis; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology*; D009538:Nicotine / Q000502:physiology; D011950:Receptors, Cholinergic / Q000502:physiology
D011950:Receptors, Cholinergic; D009538:Nicotine; D009116:Muscarine; D000109:Acetylcholine