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Brain Pathology

Laboratory of Ion Channel Pathophysiology

Hiroaki Misono,Ph.D.
The functioning of the brain relies critically on the precise control of electrical excitability of billions of neurons, which are interconnected. However, in certain cases, the brain fails to effectively regulate neuronal excitability and falls into pathological conditions such as stroke and epilepsy. Controlling electrical excitability is a major role of voltage-gated potassium (Kv) channels by counteracting membrane depolarization.

Neurons express wide varieties of Kv channels, either on the somata, dendrites, or axons. These potassium channels act to achieve rapid and precise control of the local and global membrane excitability. In doing so, they effectively regulate the overall input-output relationship between synaptic stimuli to dendrites and neurotransmitter release from axon terminals. Therefore, altering the surface density, location, or functional characteristics of Kv channels profoundly affects neuronal signaling. The goal of my research is to understand the molecular basis of the constitutive and regulated mechanisms that dynamically change the localization and function of Kv channels, and how these impact the regulation of membrane excitability in brain neurons and thereby determine animal behaviors in health and disease.
Hiroaki Misono,Ph.D.

Research topics

  1. Molecular mechanisms of vesicular trafficking of ion channels in neurons (live-cell imaging of protein trafficking)
  2. Kv channels in the regulation of sleep (EEG recording in gene knockout mice)
  3. Homeostatic regulation of neuronal excitability by Kv channel conductances in health and disease (patch-clamp recording and slice electrophysiology)

Selected publications

  1. Hirono, M.*, Watanabe, S., Karube, F., Fujiyama, F., Kawahara, S., Nagao, S., Yanagawa, Y., and Misonou, H. (2018) Perineuronal nets in the deep cerebellar nuclei regulate GABAergic transmission and delay eyeblink conditioning. Journal of Neuroscience, in press.
  2. Jensen, C.S., Watanabe, S., Stas, J.I., Klaphaak, J., Yamane, A., Schmitt, N., Olesen, S.P.O., Trimmer, J.S., Rasmussen, H.B., and Misonou, H.* (2017) Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Non-Conventional Secretory Pathway. Journal of Neuroscience 37, 11523-11536.
  3. Hirono M., Ogawa Y., Misono K., Zollinger D.R., Trimmer J.S., Rasband M.N., and Misonou H.* (2015) BK channels localize to the paranodal junction and regulate action potentials in myelinated axons of cerebellar Purkinje cells. Journal of Neuroscience 35, 7082-7094.
  4. Jensen C.S., Watanabe S., Rasmussen, H.B., Schmitt, N., Olesen, S.P., Frost, N.A., Blanpied, T.A., and Misonou H.* (2014) Specific Sorting and Post-Golgi trafficking of Dendritic Potassium Channels in Living Neurons. Journal of Biological Chemistry 289, 10566-10581.
  5. Hermanstyne T.O., Subedi K., Li W.W., Hoffman G.E., Meredith A.L., Mong J.A., and Misonou H.* (2013) Kv2.2: A novel molecular target to study the role of basal forebrain GABAergic neurons in the sleep-wake cycle. Sleep 36, 1839-1848.
  6. Kihira, Y., Hermanstyne, T.O., and Misonou H.* (2010) Formation of heteromeric Kv2 channels in mammalian brain neurons. Journal of Biological Chemistry 285, 15048-15055.
  7. Misonou H.*, Thompson, S.M., and Cai, X. (2008) Dynamic regulation of the Kv2.1 voltage-gated potassium channel during brain ischemia through neuroglial interaction. Journal of Neuroscience 28, 8529-8538.
  8. Misonou H., Menegola, M., Mohapatra, D.P., Guy, L.K., Park, K.S., and Trimmer, J.S.*(2006) Biodirectional activity-dependent regulation of neuronal potassium channel phosphorylation. Journal of Neuroscience 26, 13505-13514.
  9. Misonou H.*, Menegola, M., Mohapatra, D.P., and 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, 11184-11193.
  10. Misonou H.*, Mohapatra, D.P., Park, E.W., Leung, V., Zhen, D., Misonou, K., Anderson, A.E., and Trimmer, J.S. (2004) Regulation of ion channel localization and phosphorylation by neuronal activity. Nature Neuroscience 7, 711-718.


Hiroaki Misono, Ph.D. (Principal investigator, Professor)
Moritoshi Hirono, Ph.D. (Research associate professor)
Shoji Watanabe, Ph.D. (Research assistant professor)


Misono Lab


1-3 Tatara Miyakodani, Kyotanabe-shi, Kyoto 610-0394 Japan
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