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The Journal of Neuroscience, September 15, 1998, 18(18):7200-7215

Temperature-Sensitive Neuromuscular Transmission in Kv1.1 Null Mice: Role of Potassium Channels under the Myelin Sheath in Young Nerves

Lei Zhou¹, Chuan-Li Zhang¹, Albee Messing², and Shing Yan Chiu¹

¹ Department of Physiology, University of Wisconsin School of Medicine, ² Department of Pathobiological Sciences, School of Veterinary Medicine, and the Waisman Center, University of Wisconsin, Madison, Wisconsin 53706

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.

Key words: potassium channel gene; homologous recombination; myelinated nerves; end plate; nerve conduction; mouse

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18187200-16$05.00/0

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