Wade John Joseph, Breslin Kevin, Wong-Lin KongFatt, Harkin Jim, Flanagan Bronac, Van Zalinge Harm, Hall Steve, Dallas Mark, Bithell Angela, Verkhratsky Alexei, McDaid Liam
Computational Neuroscience and Neural Engineering (CNET) Research Team, Intelligent Systems Research Centre, Ulster University, Derry, United Kingdom.
Neural Systems and Neurotechnology Research Team, Intelligent Systems Research Centre, Ulster University, Derry, United Kingdom.
Front Cell Neurosci. 2019 May 7;13:185. doi: 10.3389/fncel.2019.00185. eCollection 2019.
It has recently been proposed using a multi-compartmental mathematical model that negatively fixed charged membrane-associated sites constrain the flow of cations in perisynaptic astroglial processes. This restricted movement of ions between the perisynaptic cradle (PsC), principal astroglial processes and the astrocyte soma gives rise to potassium (K) and sodium (Na) microdomains at the PsC. The present paper extends the above model to demonstrate that the formation of an Na microdomain can reverse the Na/Ca exchanger (NCX) thus providing an additional source of calcium (Ca) at the PsC. Results presented clearly show that reversal of the Na/Ca exchanger is instigated by a glutamate transporter coupled increase in concentration of cytoplasmic [Na] at the PsC, which and instigates Ca influx through the NCX. As the flow of Ca along the astrocyte process and away from the PsC is also constrained by Ca binding proteins, then a Ca microdomain forms at the PsC. The paper also serves to demonstrate that the EAAT, NKA, and NCX represent the minimal requirement necessary and sufficient for the development of a Ca microdomain and that these mechanisms directly link neuronal activity and glutamate release to the formation of localized Na and Ca microdomains signals at the PsC. This local source of Ca can provide a previously underexplored form of astroglial Ca signaling.
最近有人提出使用一种多室数学模型，该模型认为带负电的固定膜相关位点会限制突触周围星形胶质细胞突起中阳离子的流动。离子在突触周围支架（PsC）、主要星形胶质细胞突起和星形胶质细胞胞体之间的这种受限移动，在PsC处产生了钾（K）和钠（Na）微区。本文扩展了上述模型，以证明Na微区的形成可以使钠钙交换体（NCX）逆转，从而在PsC处提供额外的钙（Ca）来源。所呈现的结果清楚地表明，PsC处谷氨酸转运体偶联导致细胞质[Na]浓度升高，从而促使钠钙交换体逆转，进而促使Ca通过NCX内流。由于Ca沿着星形胶质细胞突起并远离PsC的流动也受到Ca结合蛋白的限制，因此在PsC处形成了一个Ca微区。本文还旨在证明，兴奋性氨基酸转运体（EAAT）、钠钾ATP酶（NKA）和钠钙交换体（NCX）是Ca微区形成所必需且充分的最低要求，并且这些机制直接将神经元活动和谷氨酸释放与PsC处局部Na和Ca微区信号的形成联系起来。这种局部Ca来源可以提供一种以前未被充分探索的星形胶质细胞Ca信号形式。
