Acetylcholine (ACh) caused various patterns of change in the intracellular Ca2+concentration ([Ca2+]i) in cultured rat hippocampal neurons. We studied the underlying mechanisms of the [Ca2+]ichanges with simultaneous recording of [Ca2+iand membrane potential/current. In most cases, [Ca2+]irise was accompanied by a membrane depolarization. The [Ca2+]ichange was significantly reduced when the membrane was voltage clamped, which implies that most of the [Ca2+]irise results from the Ca2+influx through the voltate-gated Ca2+channel activated by the membrane depolarization. The membrane depolarizations were classified into two types, one associated with membrane conductance decrease and the other associated with membrane conductance increase. The former results from potassium conductance ((gK+) decrease, and the latter may result from the activation of a Na+-permeable channel. However, [Ca2+]ielevation was also observed in some neurons showing membrane hyperpolarization in response to ACh. This seems to show that ACh liberates Ca2+from the intracellular Ca2+store, resulting in the activation of a calcium-dependent K+channel (KCa). The variations of ACh in the hippocampal neurons seem to result from a variety of muscarinic acetylcholine receptors and various species of ion channels governed by those receptors. © 1990.
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