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胆碱能去极化可募集袋状细胞神经元中的持续钙电流。

Cholinergic depolarization recruits a persistent Ca current in bag cell neurons.

机构信息

Department of Biomedical and Molecular Sciences, Experimental Medicine Graduate Program, Queen's University, Kingston, Ontario, Canada.

出版信息

J Neurophysiol. 2023 May 1;129(5):1045-1060. doi: 10.1152/jn.00429.2022. Epub 2023 Mar 29.

Abstract

Many behaviors and types of information storage are mediated by lengthy changes in neuronal activity. In bag cell neurons of the hermaphroditic sea snail , a transient cholinergic synaptic input triggers an ∼30-min afterdischarge. This causes these neuroendocrine cells to release egg laying hormone and elicit reproductive behavior. When acetylcholine is pressure-ejected onto a current-clamped bag cell neuron, the evoked depolarization is far longer than the current evoked by acetylcholine under voltage clamp, suggesting recruitment of another conductance. Our earlier studies found bag cell neurons to display a voltage-dependent persistent Ca current. Hence, we hypothesized that this current is activated by the acetylcholine-induced depolarization and sought a selective Ca current blocker. Rapid Ca current evoked by 200-ms depolarizing steps in voltage-clamped cultured bag cell neurons demonstrated a concentration-dependent sensitivity to Ni, Co, Zn, and verapamil but not Cd or ω-conotoxin GIVa. Leak subtraction of Ca current evoked by 10-s depolarizing steps using the IC (concentration required to eliminate maximal current) of Ni, Co, Zn, or verapamil revealed persistent Ca current, demonstrating persistent current block. Only Co and Zn did not suppress the acetylcholine-induced current, although Zn appeared to impact additional channels. When Co was applied during an acetylcholine-induced depolarization, the amplitude was reduced; furthermore, protein kinase C activation, previously established to enhance the persistent Ca current, extended the depolarization. Therefore, the persistent Ca current sustains the acetylcholine-induced depolarization and may translate brief cholinergic input into afterdischarge initiation. This could be a general mechanism of triggering long-term change in activity with a short-lived input. Ionotropic acetylcholine receptors mediate brief synaptic communication, including in bag cell neurons of the sea snail . However, this study demonstrates that cholinergic depolarization can open a voltage-gated persistent Ca current, which extends the bag cell neuron response to acetylcholine. Bursting in these neuroendocrine cells results in hormone release and egg laying. Thus, this emphasizes the role of ionotropic signaling in reaching a depolarized level to engage Ca influx and perpetuating the activity necessary for behavior.

摘要

许多行为和信息存储类型都受到神经元活动的长时间变化的调节。在雌雄同体的海蜗牛的袋状细胞神经元中,短暂的胆碱能突触输入引发约 30 分钟的后放电。这导致这些神经内分泌细胞释放产卵激素并引发生殖行为。当乙酰胆碱被压力喷射到电流箝位的袋状细胞神经元上时,诱发的去极化远长于电压箝位下乙酰胆碱诱发的去极化,这表明另一种电导被募集。我们之前的研究发现袋状细胞神经元显示出电压依赖性持久钙电流。因此,我们假设这种电流是由乙酰胆碱诱导的去极化激活的,并寻找一种选择性的钙电流阻断剂。在电压箝位培养的袋状细胞神经元中,200ms 去极化步骤诱发的快速钙电流对 Ni、Co、Zn 和维拉帕米表现出浓度依赖性敏感性,但对 Cd 或 ω-芋螺毒素 GIVa 没有敏感性。使用 Ni、Co、Zn 或维拉帕米的 IC(消除最大电流所需的浓度)对 10s 去极化步骤诱发的钙电流进行泄漏减法,显示出持久钙电流,表明持久电流阻断。只有 Co 和 Zn 没有抑制乙酰胆碱诱导的电流,尽管 Zn 似乎影响了其他通道。当 Co 在乙酰胆碱诱导的去极化过程中被应用时,幅度降低;此外,先前已建立的蛋白激酶 C 激活增强了持久钙电流,延长了去极化。因此,持久钙电流维持乙酰胆碱诱导的去极化,并可能将短暂的胆碱能输入转化为后放电的起始。这可能是一种将短暂的输入转化为活动的长期变化的一般机制。离子型乙酰胆碱受体介导短暂的突触通讯,包括在海蜗牛的袋状细胞神经元中。然而,这项研究表明,胆碱能去极化可以打开电压门控的持久钙电流,从而延长袋状细胞神经元对乙酰胆碱的反应。这些神经内分泌细胞的爆发导致激素释放和产卵。因此,这强调了离子型信号在达到去极化水平以参与钙内流并维持行为所需的活动中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe62/11918274/db9d2edd8b41/jn-00429-2022r01.jpg

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