title: Ionic mechanisms of cholinergic excitation in mammalian hippocampal pyramidal cells.
abstract: Intracellular recordings from CA1 hippocampal pyramidal neurons were obtained using the in vitro hippocampal slice preparation. Responses to ACh were monitored in the presence of blockers of voltage-dependent conductances including Mn2+, TTX and Ba2+. When Mn2+ was used to block voltage-dependent Ca conductance and possible indirect presynaptic cholinergic actions, ACh still induced a significant voltage-sensitive increase in apparent input resistance (Ra) (29%), but only an insignificant depolarization of membrane potential (Vm). When both voltage-dependent Ca and Na conductances were blocked by application of Mn2+ and TTX, respectively, ACh produced voltage-dependent increases in Ra (31%) without significant depolarization. In solutions containing TTX alone, ACh produced voltage-sensitive increases in Ra (32%) as well as a significant depolarization (6.2 +/- 3.1 mV (S.D.)). ACh transiently blocked the conductance increase which followed presumed Ca spikes, suggesting an action on the Ca-activated K-dependent conductance. The effects of Ba2+ application (100-200 microM) on Ra mimicked those of ACh. When ACh was applied to neurons in the presence of Ba2+, Ra remained unchanged, although Vm depolarization of 5-15 mV was still seen. The data indicate that ACh decreases both a voltage-dependent K conductance (distinct from that of the delayed rectifier) and a Ca-activated K conductance. Muscarinic cholinergic depolarization occurs as a result of blockade of K conductance, and is mediated by voltage-dependent Ca and Na conductances, and perhaps by presynaptic actions.
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002799:Cholinergic Fibers / Q000502:physiology*; D046508:Culture Techniques; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008345:Manganese / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D011976:Receptors, Muscarinic; D001464:Barium; D008345:Manganese; D013779:Tetrodotoxin; D012964:Sodium; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium