Effects of cytoskeletal modifications on Ca2+ influx after cerebral ischemia

Abstract

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+)](i) increase in response to K(+) (30 mM) depolarization was 33% higher than in wild-type. After transient focal cerebral ischemia K(+)-induced [Ca(2+)](i) 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+)](i) 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+)](i) increase in vitro. Hence, presynaptic Ca(2+) influx and subsequently neuronal vulnerability are attenuated by increased and are aggravated by decreased F-actin depolymerization.