Cytoskeleton mediates inhibition of the fast Na+ current in respiratory brainstem neurons during hypoxia.
Whole-cell Na+ currents (INa) were recorded in inspiratory neurons in a medullary slice preparation from neonatal mouse that contains the functional respiratory network. Hypoxia and metabolic poisoning with KCN rapidly inhibited INa by reducing the number of Na+ channels available for opening during depolarization. Application of agents specific for G-proteins, protein kinase C and A, intracellular Ca2+ and pH did not prevent the hypoxic inhibition of INa. The effects of hypo-osmolarity and hypoxia were additive, whereas hyperosmolarity partially prevented a subsequent hypoxic inhibition of INa. Cytochalasin B and colchicine decreased, and taxol or phalloidin increased INa and reduced its hypoxic inhibition. We conclude that cytoskeleton rearrangements during hypoxia are responsible for suppression of a fast INa in brainstem respiratory neurons, which could be mediated by the uncoupling of channel inactivation gates from cytoskeletal elements.
Mironov
S L
SL
II Department of Physiology, University of Göttingen, Germany. sergej@neuro-physiol.med.uni-goettingen.de
Richter
D W
DW
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000098:blood supply / Q000166:cytology*; D002118:Calcium / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000139:chemically induced / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D011042:Poisons; D011190:Potassium Cyanide; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D012964:Sodium / Q000502:physiology*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology
D011042:Poisons; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D003571:Cytochalasin B; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D011190:Potassium Cyanide; D002118:Calcium