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T 细胞形成免疫突触时的周期性膜电位和钙离子震荡。

Periodic Membrane Potential and Ca Oscillations in T Cells Forming an Immune Synapse.

机构信息

Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.

Department of Biophysics and Cell Biology, Faculty of Dentistry, University of Debrecen, H-4032 Debrecen, Hungary.

出版信息

Int J Mol Sci. 2020 Feb 25;21(5):1568. doi: 10.3390/ijms21051568.

Abstract

The immunological synapse (IS) is a specialized contact area formed between a T cell and an antigen presenting cell (APC). Besides molecules directly involved in antigen recognition such as the TCR/CD3 complex, ion channels important in the membrane potential and intracellular free Ca concentration control of T cells are also recruited into the IS. These are the voltage-gated Kv1.3 and Ca-activated KCa3.1 K channels and the calcium release-activated Ca channel (CRAC). However, the consequence of this recruitment on membrane potential and Ca level control is not known. Here we demonstrate that the membrane potential (MP) of murine T cells conjugated with APCs in an IS shows characteristic oscillations. We found that depolarization of the membrane by current injection or by increased extracellular K concentration produced membrane potential oscillations (MPO) significantly more frequently in conjugated T cells than in lone T cells. Furthermore, oscillation of the free intracellular Ca concentration could also be observed more frequently in cells forming an IS than in lone cells. We suggest that in the IS the special arrangement of channels and the constrained space between the interacting cells creates a favorable environment for these oscillations, which may enhance the signaling process leading to T cell activation.

摘要

免疫突触(IS)是 T 细胞和抗原呈递细胞(APC)之间形成的一种特殊接触区域。除了直接参与抗原识别的分子,如 TCR/CD3 复合物外,离子通道对于 T 细胞的膜电位和细胞内游离 Ca 浓度的控制也被招募到 IS 中。这些离子通道包括电压门控 Kv1.3 和 Ca 激活的 KCa3.1 K 通道以及钙释放激活的 Ca 通道(CRAC)。然而,这种募集对膜电位和 Ca 水平控制的后果尚不清楚。在这里,我们证明了与 APC 共轭的小鼠 T 细胞的膜电位(MP)在 IS 中表现出特征性的振荡。我们发现,通过电流注入或增加细胞外 K 浓度使膜去极化会导致共轭 T 细胞中膜电位振荡(MPO)的发生频率明显高于单独的 T 细胞。此外,在形成 IS 的细胞中也可以更频繁地观察到细胞内游离 Ca 浓度的振荡。我们认为,在 IS 中,通道的特殊排列和相互作用细胞之间的受限空间为这些振荡创造了有利的环境,这可能增强导致 T 细胞激活的信号转导过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a82/7084896/52ead532df2f/ijms-21-01568-g0A1.jpg

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