title: BK Channels Localize to the Paranodal Junction and Regulate Action Potentials in Myelinated Axons of Cerebellar Purkinje Cells.
abstract: In myelinated axons, K(+) channels are clustered in distinct membrane domains to regulate action potentials (APs). At nodes of Ranvier, Kv7 channels are expressed with Na(+) channels, whereas Kv1 channels flank nodes at juxtaparanodes. Regulation of axonal APs by K(+) channels would be particularly important in fast-spiking projection neurons such as cerebellar Purkinje cells. Here, we show that BK/Slo1 channels are clustered at the paranodal junctions of myelinated Purkinje cell axons of rat and mouse. The paranodal junction is formed by a set of cell-adhesion molecules, including Caspr, between the node and juxtaparanodes in which it separates nodal from internodal membrane domains. Remarkably, only Purkinje cell axons have detectable paranodal BK channels, whose clustering requires the formation of the paranodal junction via Caspr. Thus, BK channels occupy this unique domain in Purkinje cell axons along with the other K(+) channel complexes at nodes and juxtaparanodes. To investigate the physiological role of novel paranodal BK channels, we examined the effect of BK channel blockers on antidromic AP conduction. We found that local application of blockers to the axon resulted in a significant increase in antidromic AP failure at frequencies above 100 Hz. We also found that Ni(2+) elicited a similar effect on APs, indicating the involvement of Ni(2+)-sensitive Ca(2+) channels. Furthermore, axonal application of BK channel blockers decreased the inhibitory synaptic response in the deep cerebellar nuclei. Thus, paranodal BK channels uniquely support high-fidelity firing of APs in myelinated Purkinje cell axons, thereby underpinning the output of the cerebellar cortex.
authors.affiliation: Graduate School of Brain Science, Doshisha University, Kyoto 619-0225, Japan.
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Hirono
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, and.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Neural and Pain Sciences, Dental School, University of Maryland, Baltimore, Maryland 21201.
authors.forename: Kaori
authors.identifier: http://orcid.org/0000-0001-7682-5621
authors.initials: K
authors.lastname: Misono
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, and.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Zollinger
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, California 95616.
authors.forename: James S
authors.identifier: http://orcid.org/0000-0002-6117-3912
authors.initials: JS
authors.lastname: Trimmer
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, and h_misonou@mac.com rasband@bcm.edu.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Rasband
authors.affiliation: Graduate School of Brain Science, Doshisha University, Kyoto 619-0225, Japan, Department of Neural and Pain Sciences, Dental School, University of Maryland, Baltimore, Maryland 21201, h_misonou@mac.com rasband@bcm.edu.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Misonou
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D005260:Female; D007365:Intercellular Junctions / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009924:Organ Culture Techniques; D011689:Purkinje Cells / Q000502:physiology*; D011901:Ranvier's Nodes / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels
keywords: action potential; axon; cerebellum; potassium channel