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 Ca2+ channels. Using cultured hippocampal neurons as a model system, we have demonstrated that mutant Ca2+ 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 Ca2+ channels to pain transmission and modulation in both normal and disease states.
Another area of interest is to investigate fundamental mechanisms underlying Ca2+ channel regulation of synaptic transmission. We have shown that P/Q-type Ca2+ channels occupy type-preferring ‘slots’ to mediate neurotransmitter release. We are currently exploring the molecular basis of Ca2+ 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 YQ and Tsien RW (2010). Different relationship of N- and P/Q-type Ca2+ channels to channel-interacting slots in controlling neurotransmission at cultured hippocampal synapses. J Neurosci. 30(13): 4536-4546. Full Article >
Scherrer G, Imamachi N, Ca, YQ, Contet C, Mennicken F, O’Donnel D, Kieffer BL and Basbaum AI (2009). Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Cell. 137(6): 1148-1159. Full Article >
Cao YQ (2006 Dec 15). Voltage-gated calcium channels and pain. Pain. 126 (1-3): 5-9. Full Article >
Cao YQ, Tsien RW (2005 Feb 15). Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type Ca2+ channel activity and inhibitory synaptic transmission. Proc Natl Acad Sci U S A. 102 (7): 2590-5. Full Article >
Cao YQ, Piedras-Renteria ES, Smith GB, Chen G, Harata NC, Tsien RW (2004 Aug 5). Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy. Neuron. 43 (3): 387-400. Full Article >
Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI (1998 Mar 26). Primary afferent tachykinins are required to experience moderate to intense pain. Nature. 392 (6674): 390-4. Full Article >
Yu-Qing Cao, Ph.D.
Office Location: CSRB 5524
Office Phone: 314-362-8726
Lab Phone: 314-747-4817
Campus Box: 8054