The Physiological Role of Kv channels in myelinated and demyelinated axons

Hasan Ashraf

Identification of K Channel Subtypes and Mapping of Axonal Localization

Selectivity filter Voltage Sensor in Kv channels Voltage insensitive K channels with two subclasses: inward rectifiers and 2P domain channels

 Juxtaparanodal Tripartite of Kv1.1/Kv1.2/Kv2 Nodal Kv3.1 Channels: activates at higher threshold and has fast deactivation kinetics Internodal Kir: conductance increase when membrane is hyperpolarized. Limits tetanus induced after hyperpolarization 2P Leakage Channels

Transition zones

Schematic Drawing of an Axonal Tree

Function of Kv1 Channels in Demyelination

Morphological change of exposure of the internodal axon Unmasked Kv1 channels antagonize action potential propagation across the demyelinated region Kv1.1 expression upregulated in both axons and glia

Kv Channel Localization in Remyelinating Axons

Kv 1.1 found at nodal sites 1 week after lysolecithin injection Kv 1.1 diffuses into paranodal zones during the second week as Schwann cells begin remyelination Third week shows increased immunoreactivity to Kv1 channels in the nodal region once again Kv1 channels begin to redistribute to their final locations once again after fourth week

References
Chiu, S. Y. (1982) Resting potential of a frog myelinated axon: The role of the internode. Asbtr. Soc. Neurosci. 8, 253. Chiu, S. Y., and Ritchie, J. M. (1984). On the physiological role of internodal potassium channels in the paranodal region of acutely demyelinated mammalian single nerve fibres. J. Phsyiol. 313, 415-437. Fern. R, Ransom, B. R., and Waxman, S. G. (1995) Regional differences of the axon: a review with special reference to the concept of the multiplex neuron. Brain Res. 47, 269-288. Rasband, M. N., Trimmer, J. S., Schwarts, T. L., Levinson, S. R., and Shrager, P. (1999) K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve. J Neurocytol. 28, 319-331. Zhang, C. L. and Chiu, S. Y. (2001) Computer model for action potential propagation through branch point in myelinated nerves. J. Neurophysiol. 85, 197210. Zhou, L., Zhang, C. L., Messin, A., and Chiu, S. Y. (1998) Temperature sensitive neuromuscular transmission in Kv1.1 null mice: role of potassium chanesl under the myelin sheath in young nerves. J. Neurosci. 18, 7200-7215.