Abstract
In mammalian myelinated nerves, the internodal axon that is normally concealed by the myelin sheath expresses a rich repertoire of K channel subtypes thought to be important in modulating action potential propagation. The function of myelin-covered K channels at transition zones, however, has remained unexplored. Here we show that deleting the voltage-sensitive potassium channel Kv1.1 from mice confers a marked temperature-sensitivity to neuromuscular transmission in postnatal day 14 (P14)-P21 mice. Using immunofluorescence and electrophysiology, we examined contributions of four regions of the peripheral nervous system to the mutant phenotype: the nerve trunk, the myelinated segment preceding the terminal, the presynaptic terminal membrane itself, and the muscle. We conclude that the temperature-sensitive neuromuscular transmission is accounted for solely by a deficiency in Kv1.1 normally concealed in the myelinated segments just preceding the terminal. This paper demonstrates that under certain situations of physiological stress, the functional role of myelin-covered K channels is dramatically enhanced as the transition zone at the neuromuscular junction is approached.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Age Factors
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Anesthetics, Local / pharmacology
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Animals
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Batrachotoxins / pharmacology
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Behavior, Animal / physiology
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Cold Temperature
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Curare / pharmacology
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Elapid Venoms / pharmacology
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Electric Stimulation
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Electroencephalography
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Electrophysiology
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Female
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Kv1.1 Potassium Channel
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Lidocaine / pharmacology
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Male
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Mice
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Mice, Knockout
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Motor Neurons / chemistry
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Motor Neurons / drug effects
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Motor Neurons / physiology
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Muscle, Skeletal / chemistry
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Muscle, Skeletal / innervation
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Muscle, Skeletal / physiology
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Myelin Sheath / chemistry*
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Myelin Sheath / physiology
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Neostigmine / pharmacology
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Neuromuscular Junction / drug effects
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Neuromuscular Junction / physiology*
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Neurotoxins / pharmacology
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Nicotinic Antagonists / pharmacology
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Parasympathomimetics / pharmacology
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Phrenic Nerve / chemistry
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Phrenic Nerve / physiology
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Potassium Channels / analysis
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Potassium Channels / genetics*
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Potassium Channels / metabolism
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Potassium Channels, Voltage-Gated*
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / physiology
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Sciatic Nerve / chemistry
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Sciatic Nerve / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Temperature
Substances
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Anesthetics, Local
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Batrachotoxins
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Elapid Venoms
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Kcna1 protein, mouse
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Neurotoxins
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Nicotinic Antagonists
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Parasympathomimetics
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Potassium Channels
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Potassium Channels, Voltage-Gated
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Kv1.1 Potassium Channel
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Neostigmine
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dendrotoxin
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batrachotoxinin A 20-alpha-benzoate
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Curare
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Lidocaine