Effects of cytoskeletal modifications on Ca2+ influx after cerebral ischemia.
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.
Fink
K B
KB
Department of Pharmacology, University of Bonn, Bonn, Germany. finkk@uni-bonn.de
Paehr
M
M
Djoufack
P C
PC
Weissbrich
C
C
Bösel
J
J
Endres
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D018260:Gelsolin; D019384:Nucleic Acid Synthesis Inhibitors; D014316:Tritium; D015638:Cytochalasin D; D016202:N-Methylaspartate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine