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 #
5R37MH065334-33
Application #
8461652
Study Section
Special Emphasis Panel (NSS)
Program Officer
Asanuma, Chiiko
Project Start
2001-09-01
Project End
2016-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
33
Fiscal Year
2013
Total Cost
$364,361
Indirect Cost
$124,361
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
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
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, Xi; Jan, Lily Yeh (2014) Targeting potassium channels in cancer. J Cell Biol 206:151-62
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
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
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
Lee, Hye Young; Jan, Lily Yeh (2012) Fragile X syndrome: mechanistic insights and therapeutic avenues regarding the role of potassium channels. Curr Opin Neurobiol 22:887-94
Yang, Shi-Bing; Lee, Hye Young; Young, David Matthew et al. (2012) Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity. J Mol Med (Berl) 90:575-85

Showing the most recent 10 out of 33 publications