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dc.contributorNot Applicableen_US
dc.contributor.authorQIN, FENG Principal Investigatoren_US
dc.date31-May-11en_US
dc.date2010en_US
dc.date.accessioned2011-04-18T20:57:38Zen_US
dc.date.accessioned2011-04-19T18:31:05Z
dc.date.available1-Aug-02en_US
dc.date.available2011-04-18T20:57:38Zen_US
dc.date.available2011-04-19T18:31:05Z
dc.date.issued2011-04-18T20:57:38Zen_US
dc.identifier7860284en_US
dc.identifier5R01GM065994-08en_US
dc.identifier65994en_US
dc.identifier.urihttp://hdl.handle.net/10477/1047
dc.descriptionAcids;Afferent Neurons;Analgesics;base;Biology;capsaicin receptor;Clinical;desensitization;Detection;detector;Electrophysiology (science);Goals;Heating;improved;Ion Channel;Knowledge;Mediating;Methods;Modality;Modeling;Molecular;Molecular Biology;molecular domain;Nature;Nociception;Nociceptors;Pain;Pain management;Peripheral Nerves;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;receptor;receptor function;Recovery;Regulation;Research;research study;response;Sensory;Signal Transduction;Stimulus;TRPV1 gene;Work;en_US
dc.descriptionAmount: $ 284558en_US
dc.description.abstractDESCRIPTION (provided by applicant): Pain begins with transduction at peripheral nerve terminals of specialized sensory neurons called nociceptors. Understanding how these nociceptors respond to pain-producing stimuli is a key step towards understanding the biology of pain. This research concerns ion channels underlying nociception, in particular, the cloned vanilloid receptor TRPV1. Recent studies of the channel have shown a previously unsuspected level of complexity in its function and regulation and have implicated it in detection and integration of both exogenous noxious stimuli such as heat, vanilloids and acids and endogenous proinflammatory signals. The goal of the project is to determine, at the molecular level, how the receptor functions as a versatile noxious detector and integrator in response to various stimuli, using methods of single-channel electrophysiology combined with molecular biology. The first aim will focus on the mechanisms of the polymodal activation of the channel. Experiments are proposed to determine whether the heat sensitivity is required by other stimuli to activate the channel and how the stimuli of different modality interact within the receptor. The work will also develop allosteric models that unify the polymodal gating of the channel. The second objective is to investigate the structural basis of the polymodal activation. The study will examine to what extent the gating machinery for different stimuli are separated and will delineate the molecular domains specific to each stimulus and determine their functional mechanisms. The third aim concerns the desensitization and recovery of the channel. Experiments are proposed to quantify and establish the mechanisms of the depletion of phosphatidylinositol-45-bisphosphate (PIP2) caused by activation of TRPV1, and to elucidate the nature of the desensitized states. The proposed research will improve our knowledge of nociceptive sensory transduction and will benefit clinical advances in pain therapy, in particular, the search for analgesic drugs that have an entirely new mode of action and an unprecedented selectivity for nociceptors.en_US
dc.titleMECHANISMS OF HEAT ACTIVATION AND MULTIMODAL FUNCTIONS OF VR1 RECEPTOR CHANNELSen_US
dc.typeNIH Grant Awarden_US


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