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Yu-Qing Cao, Ph.D |
Assistant Professor of Anesthesiology Washington University Pain Center B.S.
in Biochemistry (1989) Ph.D.
in Neuroscience (1999) Postdoctoral
training (2000-2005) |
Migraine is the most common neurological disease, affecting more than 10% of the general population. One of the major symptoms of migraine, the recurring headache, is highly debilitating, poorly understood and difficult to treat. Mutations in neuronal voltage-gated calcium and sodium channels as well as in Na + /K + pump have recently been identified in patients afflicted with familial hemiplegic migraine (FHM), implicating that abnormal ion flux in neurons may be responsible for migraine attacks. My research group studies the functional consequences of FHM mutations in P/Q-type Ca 2+ channels. Using cultured hippocampal neurons as a model system, we have demonstrated that mutant Ca 2+ channels are deficient in mediating neurotransmitter release compared with wild-type ones. In addition, synapses expressing mutant channels exhibit altered sensitivity to modulation by G-protein coupled receptors. We are now investigating the effects of these mutations on neuronal excitability, homeostasis as well as synaptic transmission in circuit mediating migraine headache. To address these questions, we use a multidisciplinary approach including molecular biology, electrophysiology, imaging as well as mouse genetics. In the long run, we seek to understand the contribution of voltage-gated Ca 2+ channels to pain transmission and modulation in both normal and disease states. Another area of interest is to investigate fundamental mechanisms underlying Ca 2+ channel regulation of synaptic transmission. We have shown that P/Q-type Ca 2+ channels occupy type-preferring 'slots' to mediate neurotransmitter release. We are currently exploring the molecular basis of Ca 2+ channel-slot interactions using molecular biology in combination with immunohistochemistry. Efforts will be made to systematically search for domains on P/Q-type channel that contribute to its presynaptic targeting. On the other hand we seek to identify molecular composition of 'slots' through assays for protein-protein interaction. |
Cao, Y.Q. (2006) Voltage-gated calcium channels and pain. Pain 126: 5-9. |
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Scherrer G, Tryoen-Toth P, Filliol D., Matifas A., Laustriat D., Cao Y.Q., Basbaum A., Dierich A., Vonesh J.L., Gaveriaux-Ruff C., and Kieffer B. (2006) Knockin mice expressing fluorescent delta-opioid receptors uncover G protein coupled receptor dynamics in vivo. Proceedings of the National Academy of Science 103(25): 9691-6. |
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Barrett, C.F., Cao, Y.Q. , and Tsien, R.W. (2005) Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel. Journal of Biological Chemistry 280, 24064-24071. |
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Cao, Y.Q. and Tsien, R.W. (2005) Effects of Familial Hemiplegic Migraine type 1 mutations on neuronal P/Q-type Ca 2+ channel activity and inhibitory synaptic transmission. Proceedings of the National Academy of Science 102, 2590-2595. |
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Cao , Y.Q. , Piedras-Renteria, E.S., Smith, G.B., Chen, G., Harata, N.C., and Tsien, R.W. (2004) Presynaptic Ca 2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca 2+ channelopathy. Neuron 43, 387-400. |
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Martin, W.J., Cao , Y.Q. , and Basbaum, A.I. (2004) Characterization of wide dynamic range neurons in the deep dorsal horn of the spinal cord in preprotachykinin-A null mice in vivo. Journal of Neurophysiology 91, 1945-1954. |
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Telgkamp, P., Cao , Y.Q. , Basbaum, A.I., and Ramirez, J.M. (2002) Long-term deprivation of substance P in PPT-A mutant mice alters the anoxic response of the isolated respiratory network. Journal of Neurophysiology 88, 206-213. |
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Liu, H., Cao , Y.Q. , Basbaum, A.I., Mazarati, A.M., Sankar, R., and Wasterlain, C.G. (1999) Resistance to excitotoxin-induced seizures and neuronal death in mice lacking the preprotachykinin-A gene. Proceedings of the National Academy of Science USA 96, 12096-12101. |
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Cao , Y.Q. , Mantyh, P.W., Carlson, E.J., Gillespie, A.M., Epstein, C.J., and Basbaum, A.I. (1998) Primary afferent tachykinins are required to experience moderate to intense pain. Nature 392, 390-394. |
