Fink K B, Paehr M, Djoufack P C, Weissbrich C, Bösel J, Endres M
Department of Pharmacology, University of Bonn, Bonn, Germany.
Amino Acids. 2002;23(1-3):325-9. doi: 10.1007/s00726-001-0145-z.
The fungal toxin cytochalasin D as well as endogenous gelsolin depolymerize filamentous actin which may induce dynamic uncoupling of membrane ion channels. In vitro application of cytochalasin D reduced NMDA-induced [(3)H]noradrenaline release from mouse brain neocortical slices by 38%. In gsn deficient neocortical synaptosomes Ca(2+) increase in response to K(+) (30 mM) depolarization was 33% higher than in wild-type. After transient focal cerebral ischemia K(+)-induced Ca(2+) increase in neocortical synaptosomes was 56% lower than in synaptosomes prepared from the non-ischemic contralateral hemisphere. After in vivo pretreatment with cytochalasin D 10 min before MCA occlusion K(+)-induced Ca(2+) increase in synaptosomes in vitro prepared 1 h after reperfusion from the ischemic hemisphere was only 25% lower than in contralateral synaptosomes, while cytochalasin D pretreatment in vivo did not reduce K(+)-induced Ca(2+) increase in vitro. Hence, presynaptic Ca(2+) influx and subsequently neuronal vulnerability are attenuated by increased and are aggravated by decreased F-actin depolymerization.
真菌毒素细胞松弛素D以及内源性凝溶胶蛋白可使丝状肌动蛋白解聚，这可能会诱导膜离子通道的动态解偶联。在体外应用细胞松弛素D可使NMDA诱导的小鼠脑新皮质切片中[³H]去甲肾上腺素释放减少38%。在缺乏凝溶胶蛋白的新皮质突触体中，对30 mM K⁺去极化的反应中，[Ca²⁺]i增加比野生型高33%。短暂性局灶性脑缺血后，新皮质突触体中K⁺诱导的[Ca²⁺]i增加比从非缺血对侧半球制备的突触体低56%。在大脑中动脉闭塞前10分钟用细胞松弛素D进行体内预处理后，从缺血半球再灌注1小时后体外制备的突触体中K⁺诱导的[Ca²⁺]i增加仅比对侧突触体低25%，而体内细胞松弛素D预处理并未降低体外K⁺诱导的[Ca²⁺]i增加。因此，突触前Ca²⁺内流以及随后的神经元易损性会因F-肌动蛋白解聚增加而减弱，因F-肌动蛋白解聚减少而加重。
