Excitability of Afferents Evoking the Exercise Pressor Reflex

引起运动加压反射的传入神经的兴奋性

• 批准号: 8212538
• 负责人: KEITH S ELMSLIE
• 金额: $ 47.47万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8212538
• 关键词: Action Potentials; Adult; Afferent Neurons; Agonist; Arrhythmia; Arteries; Attention; Blood Circulation; Blood Pressure; Blood flow; Bradykinin; Bradykinin Receptor; Cardiac Output; Cardiovascular system; Cells; Chest Pain; Contracts; Coronary artery; Disease; Electrophysiology (science); Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Environmental air flow; Esthesia; Exercise; Fiber; Goals; Green Fluorescent Proteins; Heart; Heart Rate; Hindlimb; In Vitro; Ion Channel; Kidney; Label; Limb structure; Mechanics; Mediating; Membrane; Metabolic; Muscle; Muscle Fibers; Myalgia; Names; Neurons; Opioid; Opioid Receptor; Oxygen; Pain; Patch-Clamp Techniques; Peptides; Peripheral; Peripheral Vascular Diseases; Physiological; Play; Promoter Regions; Property; Prostaglandins; Rattus; Reflex action; Resistance; Role; Sensory; Signal Transduction; Skeletal Muscle; Spinal Ganglia; Stimulus; Sympathetic Nervous System; System; Testing; Tetrodotoxin; Translating; Triceps Brachii Muscle; Vascular blood supply; Weight Lifting; afferent nerve; arm; artery occlusion; claudication; density; femoral artery; ganglion cell; in vivo; insight; neuromechanism; patch clamp; pressure; public health relevance; receptive field; receptor; research study; vasoconstriction; voltage

DESCRIPTION (provided by applicant): The major goal of this application is to understand the interplay between receptors and channels that control excitability of the thin fiber muscle afferents that evoke the exercise pressor reflex as well as transduce the sensation of pain. The exercise pressor reflex, which arises from the contraction of skeletal muscles, is one of the two neural mechanisms that evoke the cardiovascular adjustments to exercise. These adjustments, which serve to support the ability of skeletal muscles to contract by increasing blood flow and oxygen to exercising muscles, include reflex increases in arterial blood pressure, cardiac output and ventilation. With respect to thin fiber muscle afferents, we propose to combine the power of the in vitro whole-cell patch- clamp technique, which will determine the mechanisms of afferent excitability, with the physiological insights provided by in vivo electrophysiology, which will determine how these mechanisms translate into increased excitability. For in vitro experiments, muscle afferents will be identified by retrograde labeling DRG neurons with DiI that has been injected into the triceps surae muscles. Particular attention will be paid to afferents that have tetradotoxin resistant channels, which will identify them as group IV muscle afferents. For in vivo experiments, thin fiber triceps surae muscle afferents will be identified by their conduction velocities and their receptive fields. In both in vitro and in vivo experiments, particular attention will be paid to the effects two peptides, namely bradykinin and DAMGO, on the membrane and discharge properties of the afferents. The former peptide is expected to be stimulatory and to act on B2 receptors, whereas the latter peptide, which is a <-opioid receptor agonist, is expected to be inhibitory. The proposed experiments are anticipated to providing new information about the mechanisms effecting the excitatory of the afferents comprising the sensory arm of the exercise pressor reflex. PUBLIC HEALTH RELEVANCE: Static (i.e., weight lifting) exercise is well known to stimulate thin fiber sensory nerves, which in turn activate the sympathetic nervous system, an effect which in turn causes vasoconstriction in the heart, kidneys and the skeletal muscles. In hearts whose coronary arteries are narrowed by disease, this vasoconstriction can cause chest pain and fatal arrhythmias. Likewise, in muscles, whose arteries are narrowed by disease, exercise can cause excessive stimulation of the sensory nerves that reflexively activate the sympathetic nervous system muscle pain (i.e., claudication).

描述（由申请人提供）：本申请的主要目标是了解受体与控制薄纤维肌肉传入的兴奋性之间的相互作用，这些纤维传入引起了运动压力的反射，并传递了疼痛的感觉。肌肉肌肉收缩引起的运动式压力反射是引起心血管调整以进行运动的两种神经机制之一。这些调整可通过增加血液流量和氧气来锻炼肌肉的骨骼肌收缩的能力，包括动脉血压，心脏输出和通风的反射增加。关于薄纤维肌肉传入，我们建议将体外全细胞贴剂技术的功能结合起来，这将确定传入兴奋性的机制以及体内电生理学提供的生理见解，这将确定这些机制如何转化为增加的兴奋性。对于体外实验，将通过将DII的DRG神经元标记为DII来鉴定肌肉传入，该标记已注射到Triceps Surae肌肉中。将特别注意具有四毒素耐药通道的传入，这将识别为IV组肌肉传入。对于体内实验，将通过其传导速度及其接受场来鉴定薄纤维三头肌传入。在体外和体内实验中，将特别注意两种肽，即心动激肽和Damgo，对传入的膜和放电性能。预计前一种肽将具有刺激性并作用于B2受体，而后一种肽（一种是<-阿片受体激动剂）预计将是抑制性的。预计该提出的实验将提供有关影响构成运动式训练式感觉部门的传入兴奋剂的机制的新信息。 公共卫生相关性：众所周知的静态（即举重）运动是刺激纤维感觉神经的众所周知，这反过来激活了交感神经系统，这种作用又导致心脏，肾脏和骨骼肌的血管收缩。在冠状动脉被疾病狭窄的心脏中，这种血管收缩会导致胸痛和致命的心律不齐。同样，在动脉被疾病狭窄的肌肉中，运动会导致过度刺激感官神经，从而反射会激活交感神经系统的肌肉疼痛（即clauraudation）。