The overall goal of this application is to understand the mechanisms by which highly specific modulation of ion channel function is achieved. The first project focuses on the KCNQ family of K+-selective ion channels expressed in neurons, heart and epithelia. The proposed studies will analyze the mechanisms of ion channel modulation by a slow signaling mechanism activated by M1 muscarinic receptors. Structure-function studies will be carried out on cloned KCNQ channels expressed in a cell line to elucidate molecular determinants of their modulation. Other ion channels that respond to the unknown messenger underlying slow modulation will be identified. Candidate messengers and candidate target regions on channels will be characterized to try to identify the messenger. The second project is to study the specificity of G-protein signaling system. The proposed studies will identify the modulatory intermediates and targets of neurotransmitter action on Ca2+ channels of the pituitary-derived GH3 cell line and characterize the specificity and molecular determinants of modulation of Ca2+ channels in neurons by G-protein beta and gamma subunits. These studies should reveal biochemical mechanisms of several key intracellular signals in neurons and provide a better understanding of the biomedical processes in which modulation of channel activity are involved, which include control of heart rate, secretion from endocrine and exocrine glands, and psychiatric changes of state.
| 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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