Neurobiology of baroreceptor perikarya and afferentation

压力感受器周核和传入的神经生物学

• 批准号: 7250150
• 负责人: JOHN H SCHILD
• 金额: $ 32.11万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7250150
• 关键词: Action Potentials; Acute; Adult; Afferent Neurons; Afferent Pathways; Autonomic nervous system; Baroreflex; Blood Pressure; Brain Stem; Capsaicin; Cardiovascular Pathology; Cardiovascular system; Chemicals; Chromosome Pairing; Class; Classification; Code; Complex; Data; Dyes; Electrophysiology (science); Elements; Ensure; Environment; Epoprostenol; Exhibits; Fiber; Functional disorder; Ganglia; Gated Ion Channel; Heart; Heart Rate; Heart failure; Hypertension; In Vitro; Ion Channel; Label; Lead; Ligands; Link; Measures; Mediating; Methodology; Modality; Myxoid cyst; Nerve; Neuraxis; Neurobiology; Neurons; Nociceptors; Numbers; Pattern; Perikaryon; Peripheral; Phenotype; Physiological; Play; Preparation; Pressoreceptors; Presynaptic Terminals; Principal Investigator; Process; Property; Rattus; Reflex action; Relative (related person); Resistance; Role; Sensory; Shapes; Signal Transduction; Slice; Synapses; Synaptic Transmission; System; Tetrodotoxin; Time; Work; autonomic reflex; capsaicin receptor; insight; large-conductance calcium-activated potassium channels; neuronal cell body; novel; novel strategies; patch clamp; pressure; programs; relating to nervous system; research study; response; synergism; voltage; voltage clamp

DESCRIPTION (provided by applicant): The arterial baroreceptor (BR) reflex plays an essential role in autonomic control of the heart. Altered discharge of BR afferents occurs with hypertension and heart failure and is therefore inextricably linked to autonomic nervous system dysfunction. BR are broadly classified as myelinated or unmyelinated afferents, each exhibiting distinct discharge patterns in response to arterial pressure changes. The micromechanical environment of the peripheral termination certainly plays a role in the process of pressure transduction. However, the operational differences in sensory coding between these two functional phenotypes may also arise from unique distributions of ion channels at critical points along the afferent pathway (e.g. arterial pressoreceptor, cell body, central synapse). Unfortunately, such a bimodal demarcation belies the continuum of physiological properties exhibited by BR and makes difficult the integration of cellular and systems level observations. For example, selective recruitment of myelinated or unmyelinated BR via electrical excitation of voltage-gated ion channels (i.e. activation independent of mechanotransduction) evokes dramatically different heart rate and blood pressure reflex responses. The ionic mechanisms that contribute to the differential sensory encoding properties of myelinated and unmyelinated BR are largely unknown. Here, we use a newly developed adult rat nerve-ganglion preparation for patch clamp study of fluorescently identified aortic baroreceptor neurons which ensures unambiguous classification of sensory modality and afferent fiber type. Preliminary data are suggestive of a differential utilization of voltage- and ligand-gated ion channels that may potentially explain some of the contrasting pressure encoding properties of myelinated and unmyelinated BR. For example, neural discharge from myelinated afferents appears less dependent upon N-type Ca2+. (ICa,N)and BK-type Ca2+-activated K+ (IKCa,BK)ion channels than activity arising from unmyelinated afferents, despite voltage clamp evidence for functional coexpression of ICa,N and IKCa,BK in both phenotypes. Such differential ionic mechanisms may underlie the disparate neural encoding properties of myelinated and unmyelinated BR and could potentially influence brainstem integration of cardiovascular afferent information if similarly represented at the presynaptic terminals. These fundamental details may lead to novel pharmacological strategies in the management of cardiovascular pathologies such as acute hypertension and dysrhythmias that are well known to involve or invoke autonomic reflexes through BR activation.

描述（由申请人提供）：动脉压力感受器（BR）反射在心脏的自主控制中起重要作用。BR传入神经的放电改变发生在高血压和心力衰竭时，因此与自主神经系统功能障碍密不可分。BR大致分为有髓传入和无髓传入，每种传入对动脉压变化的反应都表现出不同的放电模式。外周末端的微力学环境在压力转换过程中确实发挥着作用。然而，这两种功能表型之间的感觉编码的操作差异也可能是由于离子通道在传入通路（例如动脉压力感受器、细胞体、中枢突触）的关键点沿着的独特分布引起的。不幸的是，这样的双峰分界掩盖了连续的生理特性所表现出的BR，并使细胞和系统水平的观察难以整合。例如，通过电压门控离子通道的电激发（即独立于机械转导的激活）选择性募集有髓鞘或无髓鞘BR引起显著不同的心率和血压反射反应。有髓和无髓BR的差异感觉编码特性的离子机制在很大程度上是未知的。在这里，我们使用一个新开发的成年大鼠神经节制备的荧光识别的主动脉压力感受器神经元，确保明确的分类的感觉方式和传入纤维类型的膜片钳研究。初步数据表明，电压门控和配体门控离子通道的差异利用可能解释了一些有髓鞘和无髓鞘BR的对比压力编码特性。例如，来自有髓鞘传入神经的神经放电似乎不太依赖于N型Ca 2+。(ICa，N）和BK型Ca 2+激活的K+（IKCa，BK）离子通道的活性高于无髓鞘传入神经的活性，尽管电压钳证据表明伊卡，N和IKCa，BK在两种表型中都有功能性共表达。这种差异的离子机制可能是有髓和无髓BR的不同神经编码特性的基础，如果在突触前末梢也有类似的表现，可能会潜在地影响心血管传入信息的脑干整合。这些基本的细节可能会导致新的药理学策略，在管理心血管疾病，如急性高血压和心律失常，众所周知，涉及或通过BR激活调用自主反射。