The long-term objectives are to study how potasslunn channels regulation contributes to neuronal signaling.
The specific aims are to understand how the dendritic voltage-gated potassium channels and G proteinactivated inwardly rectifying potassium (GIRK) channels are regulated in hippocampal neurons, and how these potassium channels contribute to neuronal signaling and synaptic plasticity. The research design involves examination of mutant mice with altered or deleted potassium channel regulatory proteins, for regulation of either the local synthesis of channels in the dendrite or the activity or kinetic properties of the channel on the cell membrane. Because the Kv1 voltage-gated potassium channels reside on both dendrites and axons, the mosaic analysis with double markers (MADM) approach will be employed to study the physiological role of dendritic Kv1 channels.

Public Health Relevance

Mental disorders may involve an imbalance between excitation and inhibition. Whereas current studies focus primarily on synaptic function, little is known about the regulation of slow synaptic inhibition or plasticity of dendritic excitability that contributes to experience-induced changes of information processing. It is therefore important to study the physiological contribution of dendritic potassium channels.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH065334-34
Application #
8660070
Study Section
Special Emphasis Panel (NSS)
Program Officer
Asanuma, Chiiko
Project Start
2001-09-01
Project End
2016-04-30
Budget Start
2014-05-28
Budget End
2015-04-30
Support Year
34
Fiscal Year
2014
Total Cost
$379,342
Indirect Cost
$129,342
Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Yadav, Smita; Oses-Prieto, Juan A; Peters, Christian J et al. (2017) TAOK2 Kinase Mediates PSD95 Stability and Dendritic Spine Maturation through Septin7 Phosphorylation. Neuron 93:379-393
Thayer, Desiree A; Yang, Shi-Bing; Jan, Yuh Nung et al. (2016) N-linked glycosylation of Kv1.2 voltage-gated potassium channel facilitates cell surface expression and enhances the stability of internalized channels. J Physiol 594:6701-6713
Huang, Xi; He, Ye; Dubuc, Adrian M et al. (2015) EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nat Neurosci 18:1236-46
Huang, Xi; Jan, Lily Yeh (2014) Targeting potassium channels in cancer. J Cell Biol 206:151-62
Hong, TingTing; Yang, Huanghe; Zhang, Shan-Shan et al. (2014) Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia. Nat Med 20:624-32
Huang, Fen; Wang, Xidao; Ostertag, Eric M et al. (2013) TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and regulates pain processing. Nat Neurosci 16:1284-90
Isacoff, Ehud Y; Jan, Lily Y; Minor Jr, Daniel L (2013) Conduits of life's spark: a perspective on ion channel research since the birth of neuron. Neuron 80:658-74
Sun, Yaping; Dong, Zhiqiang; Jin, Taihao et al. (2013) Imaging-based chemical screening reveals activity-dependent neural differentiation of pluripotent stem cells. Elife 2:e00508
Thayer, Desiree A; Jan, Yuh Nung; Jan, Lily Yeh (2013) Increased neuronal activity fragments the Golgi complex. Proc Natl Acad Sci U S A 110:1482-7
Yang, Huanghe; Kim, Andrew; David, Tovo et al. (2012) TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation. Cell 151:111-22

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