Distinct cellular expression and subcellular localization of Kv2 voltage-gated K
Kv2.1
Kv2.2
dorsal root ganglion
somatosensory neurons
voltage-gated ion channels
Journal
The Journal of comparative neurology
ISSN: 1096-9861
Titre abrégé: J Comp Neurol
Pays: United States
ID NLM: 0406041
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
revised:
07
08
2023
received:
02
03
2023
accepted:
03
10
2023
medline:
9
2
2024
pubmed:
9
2
2024
entrez:
9
2
2024
Statut:
ppublish
Résumé
The distinct organization of Kv2 voltage-gated potassium channels on and near the cell body of brain neurons enables their regulation of action potentials and specialized membrane contact sites. Somatosensory neurons have a pseudounipolar morphology and transmit action potentials from peripheral nerve endings through axons that bifurcate to the spinal cord and the cell body within ganglia including the dorsal root ganglia (DRG). Kv2 channels regulate action potentials in somatosensory neurons, yet little is known about where Kv2 channels are located. Here, we define the cellular and subcellular localization of the Kv2 paralogs, Kv2.1 and Kv2.2, in DRG somatosensory neurons with a panel of antibodies, cell markers, and genetically modified mice. We find that relative to spinal cord neurons, DRG neurons have similar levels of detectable Kv2.1 and higher levels of Kv2.2. In older mice, detectable Kv2.2 remains similar, while detectable Kv2.1 decreases. Both Kv2 subtypes adopt clustered subcellular patterns that are distinct from central neurons. Most DRG neurons co-express Kv2.1 and Kv2.2, although neuron subpopulations show preferential expression of Kv2.1 or Kv2.2. We find that Kv2 protein expression and subcellular localization are similar between mouse and human DRG neurons. We conclude that the organization of both Kv2 channels is consistent with physiological roles in the somata and stem axons of DRG neurons. The general prevalence of Kv2.2 in DRG as compared to central neurons and the enrichment of Kv2.2 relative to detectable Kv2.1 in older mice, proprioceptors, and axons suggest more widespread roles for Kv2.2 in DRG neurons.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e25575Subventions
Organisme : NIH HHS
ID : R01NS096317
Pays : United States
Informations de copyright
© 2024 Wiley Periodicals LLC.
Références
Bishop, H. I., Cobb, M. M., Kirmiz, M., Parajuli, L. K., Mandikian, D., Philp, A. M., Melnik, M., Kuja-Panula, J., Rauvala, H., Shigemoto, R., Murray, K. D., & Trimmer, J. S. (2018). Kv2 ion channels determine the expression and localization of the associated AMIGO-1 cell adhesion molecule in adult brain neurons. Frontiers in Molecular Neuroscience, 11, Article 1. https://doi.org/10.3389/fnmol.2018.00001
Bishop, H. I., Guan, D., Bocksteins, E., Parajuli, L. K., Murray, K. D., Cobb, M. M., Misonou, H., Zito, K., Foehring, R. C., & Trimmer, J. S. (2015). Distinct cell- and layer-specific expression patterns and independent regulation of Kv2 channel subtypes in cortical pyramidal neurons. Journal of Neuroscience, 35(44), 14922-14942. https://doi.org/10.1523/jneurosci.1897-15.2015
Blaine, J. T., & Ribera, A. B. (1998). Heteromultimeric potassium channels formed by members of the Kv2 subfamily. Journal of Neuroscience, 18(23), 9585-9593. https://doi.org/10.1523/jneurosci.18-23-09585.1998
Bocksteins, E. (2016). Kv5, Kv6, Kv8, and Kv9 subunits: No simple silent bystanders. Journal of General Physiology, 147(2), 105-125. https://doi.org/10.1085/jgp.201511507
Bocksteins, E., Raes, A. L., Van De Vijver, G., Bruyns, T., Van Bogaert, P.-P., & Snyders, D. J. (2009). Kv2.1 and silent Kv subunits underlie the delayed rectifier K+ current in cultured small mouse DRG neurons. American Journal of Physiology. Cell Physiology, 296(6), C1271-C1278. https://doi.org/10.1152/ajpcell.00088.2009
Cho, W. G., & Valtschanoff, J. G. (2008). Vanilloid receptor TRPV1-positive sensory afferents in the mouse ankle and knee joints. Brain Research, 1219, 59-65. https://doi.org/10.1016/j.brainres.2008.04.043
Coggeshall, R. E. (1992). A consideration of neural counting methods. Trends in Neuroscience, 15(1), 9-13. https://doi.org/10.1016/0166-2236(92)90339-a
Coggeshall, R. E., & Lekan, H. A. (1996). Methods for determining numbers of cells and synapses: A case for more uniform standards of review. Journal of Comparative Neurology, 364(1), 6-15. https://doi.org/10.1002/(SICI)1096-9861(19960101)364:1<6::AID-CNE2>3.0.CO;2-9
Cotella, D., Hernandez-Enriquez, B., Wu, X., Li, R., Pan, Z., Leveille, J., Link, C. D., Oddo, S., & Sesti, F. (2012). Toxic role of K+ channel oxidation in mammalian brain. Journal of Neuroscience, 32(12), 4133-4144. https://doi.org/10.1523/jneurosci.6153-11.2012
Dirajlal, S., Pauers, L. E., & Stucky, C. L. (2003). Differential response properties of IB(4)-positive and -negative unmyelinated sensory neurons to protons and capsaicin. Journal of Neurophysiology, 89(1), 513-524. https://doi.org/10.1152/jn.00371.2002
Dong, X., Han, S.-K., Zylka, M. J., Simon, M. I., & Anderson, D. J. (2001). A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell, 106(5), 619-632. https://doi.org/10.1016/S0092-8674(01)00483-4
Du, J., Tao-Cheng, J.-H., Zerfas, P., & Mcbain, C. J. (1998). The K+ channel, Kv2.1, is apposed to astrocytic processes and is associated with inhibitory postsynaptic membranes in hippocampal and cortical principal neurons and inhibitory interneurons. Neuroscience, 84(1), 37-48. https://doi.org/10.1016/S0306-4522(97)00519-8
Einheber, S., Zanazzi, G., Ching, W., Scherer, S., Milner, T. A., Peles, E., & Salzer, J. L. (1997). The axonal membrane protein Caspr, a homologue of neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination. Journal of Cell Biology, 139(6), 1495-1506. https://doi.org/10.1083/jcb.139.6.1495
Fletcher, E. V., Simon, C. M., Pagiazitis, J. G., Chalif, J. I., Vukojicic, A., Drobac, E., Wang, X., & Mentis, G. Z. (2017). Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy. Nature Neuroscience, 20(7), 905-916. https://doi.org/10.1038/nn.4561
Gravagna, N. G., Knoeckel, C. S., Taylor, A. D., Hultgren, B. A., & Ribera, A. B. (2008). Localization of Kv2.2 protein in Xenopus laevis embryos and tadpoles. Journal of Comparative Neurology, 510(5), 508-524. https://doi.org/10.1002/cne.21804
Ha, H. (1970). Axonal bifurcation in the dorsal root ganglion of the cat: A light and electron microscopic study. Journal of Comparative Neurology, 140(2), 227-240. https://doi.org/10.1002/cne.901400206
He, X.-H., Zang, Y., Chen, X., Pang, R.-P., Xu, J.-T., Zhou, X., Wei, X.-H., Li, Y.-Y., Xin, W.-J., Qin, Z.-H., & Liu, X.-G. (2010). TNF-α contributes to up-regulation of Nav1.3 and Nav1.8 in DRG neurons following motor fiber injury. Pain, 151(2), 266-279. https://doi.org/10.1016/j.pain.2010.06.005
Hermanstyne, T. O., Kihira, Y., Misono, K., Deitchler, A., Yanagawa, Y., & Misonou, H. (2010). Immunolocalization of the voltage-gated potassium channel Kv2.2 in GABAergic neurons in the basal forebrain of rats and mice. Journal of Comparative Neurology, 518(21), 4298-4310. https://doi.org/10.1002/cne.22457
Hwang, P. M., Fotuhi, M., Bredt, D., Cunningham, A., & Snyder, S. (1993). Contrasting immunohistochemical localizations in rat brain of two novel K+ channels of the Shab subfamily. Journal of Neuroscience, 13(4), 1569-1576. https://doi.org/10.1523/jneurosci.13-04-01569.1993
Hwang, P. M., Glatt, C. E., Bredt, D. S., Yellen, G., & Snyder, S. H. (1992). A novel K+ channel with unique localizations in mammalian brain: Molecular cloning and characterization. Neuron, 8(3), 473-481. https://doi.org/10.1016/0896-6273(92)90275-i
Irie, T. (2021). Essential role of somatic Kv2 channels in high-frequency firing in cartwheel cells of the dorsal cochlear nucleus. eNeuro, 8(3), Article ENEURO.0515-20.2021. https://doi.org/10.1523/eneuro.0515-20.2021
Jensen, C. S., Watanabe, S., Stas, J. I., Klaphaak, J., Yamane, A., Schmitt, N., Olesen, S.-P., Trimmer, J. S., Rasmussen, H. B., & Misonou, H. (2017). Trafficking of Kv2.1 channels to the axon initial segment by a novel nonconventional secretory pathway. Journal of Neuroscience, 37(48), 11523-11536. https://doi.org/10.1523/jneurosci.3510-16.2017
Johnson, B., Leek, A. N., Solé, L., Maverick, E. E., Levine, T. P., & Tamkun, M. M. (2018). Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via interaction with VAPA and VAPB. Proceedings of the National Academy of Sciences of the United States of America, 115(31), E7331-E7340. https://doi.org/10.1073/pnas.1805757115
Johnston, J., Griffin, S. J., Baker, C., Skrzypiec, A., Chernova, T., & Forsythe, I. D. (2008). Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons. The Journal of Physiology, 586(14), 3493-3509. https://doi.org/10.1113/jphysiol.2008.153734
Kihira, Y., Hermanstyne, T. O., & Misonou, H. (2010). Formation of heteromeric Kv2 channels in mammalian brain neurons. Journal of Biological Chemistry, 285(20), 15048-15055. https://doi.org/10.1074/jbc.M109.074260
Kim, K. X., & Rutherford, M. A. (2016). Maturation of NaV and Kv channel topographies in the auditory nerve spike initiator before and after developmental onset of hearing function. Journal of Neuroscience, 36(7), 2111-2118. https://doi.org/10.1523/jneurosci.3437-15.2016
King, A. N., Manning, C. F., & Trimmer, J. S. (2014). A unique ion channel clustering domain on the axon initial segment of mammalian neurons. Journal of Comparative Neurology, 522(11), 2594-2608. https://doi.org/10.1002/cne.23551
Kirmiz, M., Vierra, N. C., Palacio, S., & Trimmer, J. S. (2018). Identification of VAPA and VAPB as Kv2 channel-interacting proteins defining endoplasmic reticulum-plasma membrane junctions in mammalian brain neurons. Journal of Neuroscience, 38, 7562-7584. https://doi.org/10.1523/jneurosci.0893-18.2018
Lee, M. C., Nahorski, M. S., Hockley, J. R. F., Lu, V. B., Ison, G., Pattison, L. A., Callejo, G., Stouffer, K., Fletcher, E., Brown, C., Drissi, I., Wheeler, D., Ernfors, P., Menon, D., Reimann, F., st John Smith, E., & Woods, C. G. (2020). Human labor pain is influenced by the voltage-gated potassium channel Kv 6.4 subunit. Cell Reports, 32(3), Article 107941. https://doi.org/10.1016/j.celrep.2020.107941
Legland, D., Arganda-Carreras, I., & Andrey, P. (2016). MorphoLibJ: Integrated library and plugins for mathematical morphology with ImageJ. Bioinformatics, 32(22), 3532-3534. https://doi.org/10.1093/bioinformatics/btw413
Li, X. N., Herrington, J., Petrov, A., Ge, L., Eiermann, G., Xiong, Y., Jensen, M. V., Hohmeier, H. E., Newgard, C. B., Garcia, M. L., Wagner, M., Zhang, B. B., Thornberry, N. A., Howard, A. D., Kaczorowski, G. J., & Zhou, Y.-P. (2013). The role of voltage-gated potassium channels Kv2.1 and Kv2.2 in the regulation of insulin and somatostatin release from pancreatic islets. Journal of Pharmacology and Experimental Therapeutics, 344(2), 407-416. https://doi.org/10.1124/jpet.112.199083
Lim, S. T., Antonucci, D. E., Scannevin, R. H., & Trimmer, J. S. (2000). A novel targeting signal for proximal clustering of the Kv2.1 K+ channel in hippocampal neurons. Neuron, 25(2), 385-397. https://doi.org/10.1016/S0896-6273(00)80902-2
Liu, P. W., & Bean, B. P. (2014). Kv2 channel regulation of action potential repolarization and firing patterns in superior cervical ganglion neurons and hippocampal CA1 pyramidal neurons. Journal of Neuroscience, 34(14), 4991-5002. https://doi.org/10.1523/jneurosci.1925-13.2014
Matsuda, S., Kobayashi, N., Terashita, T., Shimokawa, T., Shigemoto, K., Mominoki, K., Wakisaka, H., Saito, S., Miyawaki, K., Saito, K., Kushihata, F., Chen, J., Gao, S.-Y., Li, C.-Y., Wang, M., & Fujiwara, T. (2005). Phylogenetic investigation of Dogiel's pericellular nests and Cajal's initial glomeruli in the dorsal root ganglion. Journal of Comparative Neurology, 491(3), 234-245. https://doi.org/10.1002/cne.20713
Misonou, H., Mohapatra, D. P., Menegola, M., & Trimmer, J. S. (2005). Calcium- and metabolic state-dependent modulation of the voltage-dependent Kv2.1 channel regulates neuronal excitability in response to ischemia. Journal of Neuroscience, 25(48), 11184-11193. https://doi.org/10.1523/jneurosci.3370-05.2005
Muennich, E. A. L., & Fyffe, R. E. W. (2004). Focal aggregation of voltage-gated, Kv2.1 subunit-containing, potassium channels at synaptic sites in rat spinal motoneurones. The Journal of Physiology, 554(Pt 3), 673-685. https://doi.org/10.1113/jphysiol.2003.056192
Newkirk, G. S., Guan, D., Dembrow, N., Armstrong, W. E., Foehring, R. C., & Spain, W. J. (2022). Kv2.1 potassium channels regulate repetitive burst firing in extratelencephalic neocortical pyramidal neurons. Cerebral Cortex, 32(5), 1055-1076. https://doi.org/10.1093/cercor/bhab266
Panzera, L. C., Johnson, B., Quinn, J. A., Cho, I. H., Tamkun, M. M., & Hoppa, M. B. (2022). Activity-dependent endoplasmic reticulum Ca(2+) uptake depends on Kv2.1-mediated endoplasmic reticulum/plasma membrane junctions to promote synaptic transmission. Proceedings of the National Academy of Sciences of the United States of America, 119(30), Article e2117135119. https://doi.org/10.1073/pnas.2117135119
Rasband, M. N., Trimmer, J. S., Schwarz, T. L., Levinson, S. R., Ellisman, M. H., Schachner, M., & Shrager, P. (1998). Potassium channel distribution, clustering, and function in remyelinating rat axons. Journal of Neuroscience, 18(1), 36-47. https://doi.org/10.1523/jneurosci.18-01-00036.1998
Regnier, G., Bocksteins, E., Van De Vijver, G., Snyders, D. J., & Van Bogaert, P.-P. (2016). The contribution of Kv2.2-mediated currents decreases during the postnatal development of mouse dorsal root ganglion neurons. Physiological Reports, 4(6), Article e12731. https://doi.org/10.14814/phy2.12731
Romer, S. H., Dominguez, K. M., Gelpi, M. W., Deardorff, A. S., Tracy, R. C., & Fyffe, R. E. W. (2014). Redistribution of Kv2.1 ion channels on spinal motoneurons following peripheral nerve injury. Brain Research, 1547, 1-15. https://doi.org/10.1016/j.brainres.2013.12.012
Sarmiere, P. D., Weigle, C. M., & Tamkun, M. M. (2008). The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ. BMC Neuroscience, 9, Article 112. https://doi.org/10.1186/1471-2202-9-112
Scannevin, R. H., Murakoshi, H., Rhodes, K. J., & Trimmer, J. S. (1996). Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel. Journal of Cell Biology, 135(6 Pt 1), 1619-1632. https://doi.org/10.1083/jcb.135.6.1619
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., Tinevez, J.-Y., White, D. J., Hartenstein, V., Eliceiri, K., Tomancak, P., & Cardona, A. (2012). Fiji: An open-source platform for biological-image analysis. Nature Methods, 9(7), 676-682. https://doi.org/10.1038/nmeth.2019
Scott, B., Leu, J., & Cinader, B. (1988). Effects of aging on neuronal electrical membrane properties. Mechanisms of Ageing and Development, 44(3), 203-214. https://doi.org/10.1016/0047-6374(88)90022-x
Shields, S. D., Ahn, H.-S., Yang, Y., Han, C., Seal, R. P., Wood, J. N., Waxman, S. G., & Dib-Hajj, S. D. (2012). Nav1.8 expression is not restricted to nociceptors in mouse peripheral nervous system. Pain, 153(10), 2017-2030. https://doi.org/10.1016/j.pain.2012.04.022
Shiers, S., Klein, R. M., & Price, T. J. (2020). Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscope in situ hybridization. Pain, 161(10), 2410-2424. https://doi.org/10.1097/j.pain.0000000000001973
Shiers, S. I., Sankaranarayanan, I., Jeevakumar, V., Cervantes, A., Reese, J. C., & Price, T. J. (2021). Convergence of peptidergic and non-peptidergic protein markers in the human dorsal root ganglion and spinal dorsal horn. Journal of Comparative Neurology, 529(10), 2771-2788. https://doi.org/10.1002/cne.25122
Sun, Z.-W., Waybright, J. M., Beldar, S., Chen, L., Foley, C. A., Norris-Drouin, J. L., Lyu, T.-J., Dong, A., Min, J., Wang, Y.-P., James, L. I., & Wang, Y. (2022). Cdyl deficiency brakes neuronal excitability and nociception through promoting Kcnb1 transcription in peripheral sensory neurons. Advanced Science, 9(10), Article e2104317. https://doi.org/10.1002/advs.202104317
Tavares-Ferreira, D., Shiers, S., Ray, P. R., Wangzhou, A., Jeevakumar, V., Sankaranarayanan, I., Cervantes, A. M., Reese, J. C., Chamessian, A., Copits, B. A., Dougherty, P. M., Gereau, R. W., Burton, M. D., Dussor, G., & Price, T. J. (2022). Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors. Science Translational Medicine, 14(632), Article eabj8186. https://doi.org/10.1126/scitranslmed.abj8186
Thapa, P., Stewart, R., Sepela, R. J., Vivas, O., Parajuli, L. K., Lillya, M., Fletcher-Taylor, S., Cohen, B. E., Zito, K., & Sack, J. T. (2021). EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues. Journal of General Physiology, 153(11), Article e202012858. https://doi.org/10.1085/jgp.202012858
Trimmer, J. S. (1991). Immunological identification and characterization of a delayed rectifier K+ channel polypeptide in rat brain. Proceedings of the National Academy of Sciences of the United States of America, 88(23), 10764-10768. https://doi.org/10.1073/pnas.88.23.10764
Tsantoulas, C., Zhu, L., Shaifta, Y., Grist, J., Ward, J. P. T., Raouf, R., Michael, G. J., & Mcmahon, S. B. (2012). Sensory neuron downregulation of the Kv9.1 potassium channel subunit mediates neuropathic pain following nerve injury. Journal of Neuroscience, 32(48), 17502-17513. https://doi.org/10.1523/jneurosci.3561-12.2012
Tsantoulas, C., Zhu, L., Yip, P., Grist, J., Michael, G. J., & Mcmahon, S. B. (2014). Kv2 dysfunction after peripheral axotomy enhances sensory neuron responsiveness to sustained input. Experimental Neurology, 251, 115-126. https://doi.org/10.1016/j.expneurol.2013.11.011
Usoskin, D., Furlan, A., Islam, S., Abdo, H., Lönnerberg, P., Lou, D., Hjerling-Leffler, J., Haeggström, J., Kharchenko, O., Kharchenko, P. V., Linnarsson, S., & Ernfors, P. (2015). Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nature Neuroscience, 18(1), 145-153. https://doi.org/10.1038/nn.3881
Valtcheva, M. V., Copits, B. A., Davidson, S., Sheahan, T. D., Pullen, M. Y., Mccall, J. G., Dikranian, K., & Gereau, R. W. T. (2016). Surgical extraction of human dorsal root ganglia from organ donors and preparation of primary sensory neuron cultures. Nature Protocols, 11(10), 1877-1888. https://doi.org/10.1038/nprot.2016.111
Vierra, N. C., O'dwyer, S. C., Matsumoto, C., Santana, L. F., & Trimmer, J. S. (2021). Regulation of neuronal excitation-transcription coupling by Kv2.1-induced clustering of somatic L-type Ca(2+) channels at ER-PM junctions. Proceedings of the National Academy of Sciences of the United States of America, 118(46), Article e2110094118. https://doi.org/10.1073/pnas.2110094118
Vullhorst, D., Mitchell, R. M., Keating, C., Roychowdhury, S., Karavanova, I., Tao-Cheng, J.-H., & Buonanno, A. (2015). A negative feedback loop controls NMDA receptor function in cortical interneurons via neuregulin 2/ErbB4 signalling. Nature Communications, 6, Article 7222. https://doi.org/10.1038/ncomms8222
Wang, H., & Zylka, M. J. (2009). Mrgprd-expressing polymodal nociceptive neurons innervate most known classes of substantia gelatinosa neurons. Journal of Neuroscience, 29(42), 13202-13209. https://doi.org/10.1523/jneurosci.3248-09.2009
Wangzhou, A., Mcilvried, L. A., Paige, C., Barragan-Iglesias, P., Shiers, S., Ahmad, A., Guzman, C. A., Dussor, G., Ray, P. R., Gereau, R. W., & Price, T. J. (2020). Pharmacological target-focused transcriptomic analysis of native vs cultured human and mouse dorsal root ganglia. Pain, 161(7), 1497-1517. https://doi.org/10.1097/j.pain.0000000000001866
Zheng, Y., Liu, P., Bai, L., Trimmer, J. S., Bean, B. P., & Ginty, D. D. (2019). Deep sequencing of somatosensory neurons reveals molecular determinants of intrinsic physiological properties. Neuron, 103(4), 598.e7-616.e7. https://doi.org/10.1016/j.neuron.2019.05.039