Excitability of afferents evoking the exercise pressor reflex

引起运动升压反射的传入神经的兴奋性

基本信息

批准号：
9246472
负责人：
KEITH S ELMSLIE
金额：
$ 64.39万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9246472
关键词：
Action Potentials Affect Afferent Neurons Arteries Attention Attenuated Blood flow Bradykinin Cardiac Output Cardiovascular system Cells Chronic Contracts Disease Electrophysiology (science)Environmental air flow Esthesia Exercise FDA approved Fiber Funding G-substrate GTP-Binding Proteins Goals Heart Heart Rate Hindlimb In Vitro Injectable Ion Channel Kidney Label Laboratories Limb structure Mechanics Mediating Metabolic Muscle Muscle Fibers Myalgia Names Natural experiment Nerve Neurons Opioid Opioid Receptor Oxygen P2X-receptor Pain Patch-Clamp Techniques Patients Peripheral Peripheral Vascular Diseases Pertussis Toxin Physiological Play Prostaglandins Protein Subunits Rattus Reflex action Role Sensory Signal Transduction Signaling Protein Skeletal Muscle Stimulus Sympathetic Nervous System Systemic blood pressure TRPV1 gene Tetrodotoxin Thinness Tissues Translating Triceps Brachii Muscle Vascular blood supply afferent nerve arm attenuation claudication delta opioid receptor experimental study femoral artery in vivo insight neuromechanism pressure public health relevance receptive field receptor transmission process vasoconstriction voltage

项目摘要

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 (EPR) as well as transduce the sensation of pain. The EPR, which arises from contraction of skeletal muscle, is one of two key neural mechanisms that evoke the cardiovascular adjustments to exercise. These adjustments, which support the ability of skeletal muscles to contract by increasing blood flow and oxygen to exercising muscles, include increases in systemic blood pressure, cardiac output and ventilation. With respect to the thin fiber muscle afferents that mediate the EPR, we combine the power of the in vitro whole-cell patch-clamp technique to determine the mechanisms of afferent excitability, with the physiological insights provided by in vivo electrophysiology to 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 small afferent neurons that express channels known to elicit the EPR (e.g. ASIC, TRPV1, P2X and TRPA1). 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, we will concentrat on the mechanisms by which two receptors, the µ opioid (Aim 1) and δ-opioid (Aim 2) receptors, inhibit the EPR. Additional experiments will investigate the role of two voltage depend ion channels, KV7 (Aim 3) and NaV1.7 (Aim 4) in controlling the excitability of the EPR. The proposed experiments are natural extensions from those of our previous funding period and will greatly increase our understanding of the mechanisms affecting the excitatory afferents comprising the sensory arm of the EPR.

描述（由应用程序提供）：本应用程序的主要目标是了解接收器与控制薄纤维肌肉传入的刺激性的接收器之间的相互作用，这些纤维传入引起了运动式压力反射（EPR）以及传递疼痛的感觉。 EPR是由骨骼肌收缩引起的，是引起心血管调整以进行运动的两种关键神经元机制之一。这些调整支持骨骼肌通过增加血流和氧气运动肌肉收缩的能力，包括增加系统性血压，心脏输出和通风。关于介导EPR的薄纤维肌肉传入，我们结合了体外全细胞贴片钳技术的功能，以确定传入兴奋的机制，并与体内电生理学提供的物理见解，以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。将特别关注小型传入神经元，这些神经元表达已知引起EPR的通道（例如ASIC，TRPV1，P2X和TRPA1）。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，我们将集中于两个受体，即µ阿片类药物（AIM 1）和δ-阿片类药物（AIM 2）受体，抑制EPR。其他实验将研究两个电压依赖离子通道的作用，KV7（AIM 3）和NAV1.7（AIM 4）在控制EPR的兴奋性中的作用。提出的实验是我们以前的资金期间的自然扩展，将大大提高我们对影响EPR感官臂的兴奋传入机制的理解。