Calcium transients in intramuscular interstitial cells of Cajal of the murine gastric fundus and their regulation by neuroeffector transmission.
Calcium transients in intramuscular interstitial cells of Cajal of the murine gastric fundus and their regulation by neuroeffector transmission.
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小鼠胃底卡哈尔肌内间质细胞中的钙瞬变及其神经效应器传递的调节。
DOI：
10.1113/jp282876
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ward,SeanM
中科院分区：
文献类型：
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作者：
Hwang,SungJin;Drumm,BernardT;Kim,MinKyung;Lyu,JuHyeong;Baker,Sal;Sanders,KentonM;Ward,SeanM
摘要肠道神经传递对于协调整个胃肠道（GI）的运动至关重要。然而，对于负责这些神经输入的转导的细胞存在相当大的争议。在本研究中，利用细胞特异性钙生物传感器GCaMP 6 f，检查了肌内ICC（ICC‐IM）对运动神经输入的自发活动和神经效应器反应。在神经刺激过程中同时进行细胞内微电极记录和高速视频成像，以揭示细胞内Ca 2+变化与神经刺激后连接后电反应之间的时间关系。ICC‐IM高度活跃，从单个ICC‐IM中的多个独立位点产生随机发生的细胞内Ca 2 +‐瞬变。单个ICC‐IM或相邻ICC‐IM之间未夹带Ca 2+瞬变。肠运动神经元的激活产生了显性抑制反应，消除了ICC‐IM中的Ca 2+瞬变。这种抑制反应之前通常是Ca 2+瞬变的总和，导致Ca 2+的整体升高。个体ICC-IM对神经刺激的反应是Ca 2+整体升高，随后抑制Ca 2+瞬变。一氧化氮合酶拮抗剂1-NNA可阻断Ca 2 +-瞬变的抑制作用。毒蕈碱拮抗剂阿托品可抑制细胞内Ca ~（2+）的整体升高。同时进行的细胞内微电极记录和视频成像显示，Ca 2+的升高与快速兴奋性连接电位和抑制性连接电位对Ca 2+瞬变的抑制在时间上相关。这些数据支持的前提下，串行神经支配的ICC‐IM兴奋性和抑制性神经效应传递在近端stomach.Key pointsThe细胞负责介导肠道神经效应传递仍然存在争议。在胃中，肌内Cajal间质细胞（ICC‐IM）是第一个被报道接受胆碱能和氮能神经输入的ICC。利用细胞特异性钙生物传感器GCaMP 6 f，检测ICC‐IM的活性和神经效应器反应。ICC‐IM高度活跃，产生随机的细胞内Ca 2 +‐瞬变。刺激肠运动神经可消除ICC‐IM中的Ca 2 +‐瞬变。这种抑制反应之前，细胞内Ca 2+的整体上升。单个ICC‐IM对神经刺激的反应是Ca 2+升高，随后抑制Ca 2 +‐瞬变。一氧化氮合酶拮抗剂1 ‐NNA阻断了对Ca 2 +‐瞬变的抑制。M受体拮抗剂阿托品可抑制细胞内Ca ~（2+）的整体升高，同时细胞内录像显示，细胞内Ca ~（2+）的整体升高和Ca ~（2+）的抑制，- 瞬变与快速兴奋性连接电位相关，随后是更持续的抑制性连接电位。所提供的数据支持ICC-IM在兴奋性和抑制性神经效应传递中的连续神经支配的前提。胃近端
AbstractEnteric neurotransmission is critical for coordinating motility throughout the gastrointestinal (GI) tract. However, there is considerable controversy regarding the cells that are responsible for the transduction of these neural inputs. In the present study, utilization of a cell‐specific calcium biosensor GCaMP6f, the spontaneous activity and neuroeffector responses of intramuscular ICC (ICC‐IM) to motor neural inputs was examined. Simultaneous intracellular microelectrode recordings and high‐speed video‐imaging during nerve stimulation was used to reveal the temporal relationship between changes in intracellular Ca2+and post‐junctional electrical responses to neural stimulation. ICC‐IM were highly active, generating intracellular Ca2+‐transients that occurred stochastically, from multiple independent sites in single ICC‐IM. Ca2+‐transients were not entrained in single ICC‐IM or between neighbouring ICC‐IM. Activation of enteric motor neurons produced a dominant inhibitory response that abolished Ca2+‐transients in ICC‐IM. This inhibitory response was often preceded by a summation of Ca2+‐transients that led to a global rise in Ca2+. Individual ICC‐IM responded to nerve stimulation by a global rise in Ca2+followed by inhibition of Ca2+‐transients. The inhibition of Ca2+‐transients was blocked by the nitric oxide synthase antagonistl‐NNA. The global rise in intracellular Ca2+was inhibited by the muscarinic antagonist, atropine. Simultaneous intracellular microelectrode recordings with video‐imaging revealed that the rise in Ca2+was temporally associated with rapid excitatory junction potentials and the inhibition of Ca2+‐transients with inhibitory junction potentials. These data support the premise of serial innervation of ICC‐IM in excitatory and inhibitory neuroeffector transmission in the proximal stomach.Key pointsThe cells responsible for mediating enteric neuroeffector transmission remain controversial. In the stomach intramuscular interstitial cells of Cajal (ICC‐IM) were the first ICC reported to receive cholinergic and nitrergic neural inputs.Utilization of a cell specific calcium biosensor, GCaMP6f, the activity, and neuroeffector responses of ICC‐IM were examined. ICC‐IM were highly active, generating stochastic intracellular Ca2+‐transients.Stimulation of enteric motor nerves abolished Ca2+‐transients in ICC‐IM. This inhibitory response was preceded by a global rise in intracellular Ca2+. Individual ICC‐IM responded to nerve stimulation with a rise in Ca2+followed by inhibition of Ca2+‐transients.Inhibition of Ca2+‐transients was blocked by the nitric oxide synthase antagonistl‐NNA. The global rise in Ca2+was inhibited by the muscarinic antagonist atropine.Simultaneous intracellular recordings with video imaging revealed that the global rise in intracellular Ca2+and inhibition of Ca2+‐transients was temporally associated with rapid excitatory junction potentials followed by more sustained inhibitory junction potentials.The data presented support the premise of serial innervation of ICC‐IM in excitatory and inhibitory neuroeffector transmission in the proximal stomach.