Volatile anesthetics block actin-based motility in dendritic spines.
Dendritic spines form the postsynaptic contact sites for most excitatory synapses in the brain. Spines occur in a wide range of different shapes that can vary depending on an animal's experience or behavioral status. Recently we showed that spines on living neurons can change shape within seconds in a process that depends on actin polymerization. We have now found that this morphological plasticity is blocked by inhalational anesthetics at concentrations at which they are clinically effective. These volatile compounds also block actin-based motility in fibroblasts, indicating that their action is independent of neuron-specific components and thus identifying the actin cytoskeleton as a general cellular target of anesthetic action. These observations imply that inhibition of actin dynamics at brain synapses occurs during general anesthesia and that inhalational anesthetics are capable of influencing the morphological plasticity of excitatory synapses in the brain.
Kaech
S
S
Friedrich Miescher Institute, P.O. Box 2543, 4002 Basel, Switzerland.
Brinkhaus
H
H
Matus
A
A
D000199:Actins / Q000235:genetics / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002725:Chloroform / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004622:Embryo, Mammalian; D004737:Enflurane / Q000494:pharmacology; D004986:Ether / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007530:Isoflurane / Q000494:pharmacology; D008733:Methoxyflurane / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D000199:Actins; D018685:Anesthetics, Inhalation; D011994:Recombinant Proteins; D004986:Ether; D008733:Methoxyflurane; D002725:Chloroform; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane