Actin-ATP hydrolysis is a major energy drain for neurons.
In cultured chick ciliary neurons, when ATP synthesis is inhibited, ATP depletion is reduced approximately 50% by slowing actin filament turnover with jasplakinolide or latrunculin A. Jasplakinolide inhibits actin disassembly, and latrunculin A prevents actin assembly by sequestering actin monomers. Cytochalasin D, which allows assembly-disassembly, but only at pointed ends, is less effective in conserving ATP. Ouabain, an Na(+)-K(+)-ATPase inhibitor, and jasplakinolide both prevent approximately 50% of the ATP loss. When applied together, they completely prevent ATP loss over a period of 20 min, suggesting that filament stabilization reduces ATP consumption by decreasing actin-ATP hydrolysis directly rather than indirectly by modulating the activity of Na(+)-K(+)-ATPase, a major energy consumer.
Bernstein
Barbara W
BW
Department of Biochemistry and Molecular Biology and the Program in Molecular, Cellular, and Integrative Neuroscience, Colorado State University, Fort Collins, Colorado 80523-1870, USA. bwb@lamar.colostate.edu
Bamburg
James R
JR
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002642:Chick Embryo; D047630:Depsipeptides; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006868:Hydrolysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D012964:Sodium / Q000032:analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D013844:Thiazoles; D053778:Thiazolidines; C057531:jasplakinolide; D010042:Ouabain; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; C037067:latrunculin A; D002118:Calcium