Variation in the pattern of [Ca²⁺]_i change induced by acetylcholine in cultured hippocampal neurons

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⁺]_i changes with simultaneous recording of [Ca²⁺ _i and membrane potential/current. In most cases, [Ca²⁺]_i rise was accompanied by a membrane depolarization. The [Ca²⁺]_i change was significantly reduced when the membrane was voltage clamped, which implies that most of the [Ca²⁺]_i rise 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⁺]_i elevation 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 (K_Ca). 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.