The long-term objectives are to clarify electrical and chemical mechanisms of signaling in the nervous system through rigorous and quantitative thinking about ionic channels, receptors, G proteins, second messengers, and transmitter turnover. The primary methods will be whole-cell patch-clamp recording with many biochemical interventions using isolated single cells. Signaling mechanisms that modulate currents in voltage-gated Ca channels and other channels will be characterized in mammalian superior cervical ganglion cells and medium spiny neurons. This will include actions of monoamine transmitters, GABA, peptides, and cannabinoids. Such studies will inventory and describe a network of interacting intracellular signals coupling between receptors and ionic channels that they control in neurons. They will give more quantitative information on the speed and intensity of pathways mediated by different second messenger systems, and will eventually allow theoretical reconstruction of neuronal responses. The radius of action and the rate of uptake of monoamine transmitters will be determined by voltammetry and anatomical studies to gauge the specificity of central signaling pathways. The biophysical properties of various understudied voltage-gated and ligand-gated channels will be determined. The results will bear on the basic neuroscience of signaling. The modulatory actions to be studied are disturbed in schizophrenia, Parkinsonism, and mood and emotional disorders.
| Jung, Seung-Ryoung; Deng, Yi; Kushmerick, Christopher et al. (2018) Minimizing ATP depletion by oxygen scavengers for single-molecule fluorescence imaging in live cells. Proc Natl Acad Sci U S A 115:E5706-E5715 |
| Yu, Haijie; Seo, Jong Bae; Jung, Seung-Ryoung et al. (2015) Noradrenaline upregulates T-type calcium channels in rat pinealocytes. J Physiol 593:887-904 |
| Hille, Bertil; Dickson, Eamonn J; Kruse, Martin et al. (2015) Phosphoinositides regulate ion channels. Biochim Biophys Acta 1851:844-56 |
| Hille, Bertil; Dickson, Eamonn; Kruse, Martin et al. (2014) Dynamic metabolic control of an ion channel. Prog Mol Biol Transl Sci 123:219-47 |
| Yoon, Jin-Young; Jung, Seung-Ryoung; Hille, Bertil et al. (2014) Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes. Am J Physiol Cell Physiol 306:C726-35 |
| Dickson, Eamonn J; Falkenburger, Björn H; Hille, Bertil (2013) Quantitative properties and receptor reserve of the IP(3) and calcium branch of G(q)-coupled receptor signaling. J Gen Physiol 141:521-35 |
| Falkenburger, Björn H; Dickson, Eamonn J; Hille, Bertil (2013) Quantitative properties and receptor reserve of the DAG and PKC branch of G(q)-coupled receptor signaling. J Gen Physiol 141:537-55 |
| Kim, Mean-Hwan; Seo, Jong Bae; Burnett, Lindsey A et al. (2013) Characterization of store-operated Ca2+ channels in pancreatic duct epithelia. Cell Calcium 54:266-75 |
| Kruse, Martin; Hille, Bertil (2013) The phosphoinositide sensitivity of the K(v) channel family. Channels (Austin) 7:530-6 |
| Dickson, Eamonn J; Duman, Joseph G; Moody, Mark W et al. (2012) Orai-STIM-mediated Ca2+ release from secretory granules revealed by a targeted Ca2+ and pH probe. Proc Natl Acad Sci U S A 109:E3539-48 |
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