Temperature-sensitive neuromuscular transmission in Kv1.1 null mice: role of potassium channels under the myelin sheath in young nerves.
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.
Zhou
L
L
Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706, USA.
Zhang
C L
CL
Messing
A
A
Chiu
S Y
SY
D000367:Age Factors; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology; D003080:Cold Temperature; D003472:Curare / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation; D004569:Electroencephalography; D004594:Electrophysiology; D005260:Female; D051662:Kv1.1 Potassium Channel; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000294:innervation / Q000502:physiology; D009186:Myelin Sheath / Q000737:chemistry* / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010791:Phrenic Nerve / Q000737:chemistry / Q000502:physiology; D015221:Potassium Channels / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D012584:Sciatic Nerve / Q000737:chemistry / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013696:Temperature
D000779:Anesthetics, Local; D001496:Batrachotoxins; D004546:Elapid Venoms; C496947:Kcna1 protein, mouse; D009498:Neurotoxins; D018733:Nicotinic Antagonists; D010277:Parasympathomimetics; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; D009388:Neostigmine; C020273:dendrotoxin; C031775:batrachotoxinin A 20-alpha-benzoate; D003472:Curare; D008012:Lidocaine