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The role of TRPM8 and Nav1.8 channels in cold tolerance of hibernators

TRPM8和Nav1.8通道在冬眠动物耐冷能力中的作用

基本信息

批准号：
9026719
负责人：
Elena Gracheva
金额：
$ 35.55万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9026719
关键词：
Action Potentials Acute Affect Analgesics Animal Model Animals Area Behavioral Paradigm Bioinformatics Biological Blood Body Temperature Calcium Cations Cellular biology Data Detection Development Drops Drug or chemical Tissue Distribution Electrodes Electrophysiology (science)Environment Esthesia Event Ganglia Genomics Glean Goals Health Heart Arrest Hibernation Human Image In Situ Hybridization Ion Channel Knowledge Laboratories Medical Menthol Modeling Modification Molecular Mus Neuraxis Neurons Outcome Pain Pathway interactions Perception Personal Satisfaction Pharmacology Phenotype Physiologic Thermoregulation Physiological Physiology Play Process Property Protein Isoforms RNA RNA Splicing Regulation Resistance Rodent Role Sensory Signal Transduction Sodium Channel Spermophilus Squirrel Stimulus Stroke System TRP channel Temperature Tetrodotoxin Therapeutic Trauma Variant allodynia base biophysical properties chemotherapy cold temperature in vivo insight natural hypothermia nerve injury novel novel strategies painful neuropathy patch clamp post stroke public health relevance ratiometric response somatosensory transcriptomics transmission process voltage voltage clamp

项目摘要

DESCRIPTION (provided by applicant): Thermosensitivity and thermotolerance are fundamental processes that affect virtually all aspects of human physiology. Human sensation of cold - ranging from refreshingly cool to unpleasant and frigid - relies on the ability of primar sensory afferents to transduce these stimuli into electrical signaling, thereby triggering adaptive biological response. Dysregulation of thermosensation underlie cold allodynia - a common hallmark of chemotherapy-, nerve injury- and post-stroke-induced neuropathic pain, in which even mild cooling can be perceived as excruciatingly painful. Despite significant medical relevance, the molecular aspects of cold sensation under normal, adaptive and pathological conditions, and the sequence of events that underlies this process still remain enigmatic and controversial. Animals that tune temperature sensitivity to the extreme provide ideal model to delineate cellular and molecular aspects of thermotolerance and temperature perception in general. We are using mammalian hibernation as a naturally-reversible model to understand these processes. Unlike the standard laboratory rodents, hibernating animals do not perceive cold temperature as uncomfortable until -2°C. This remarkable ability contributes to their unusual resistance to cold during hibernation, when the animals drop their core body temperature to 2-4°C. In this proposal, we are aiming to examine contribution of TRPM8 and Nav1.8 ion channels into cold adaptations in hibernating squirrels at the level of somatosensory system using multi-disciplinary approach, including physiology, imaging, behavioral paradigms, cell biology, differential transcriptomics, genomics and bioinformatics.