Cellular electrophysiology of vasculatures in inner ear

内耳脉管系统的细胞电生理学

• 批准号: 7151128
• 负责人: ZHI-GEN JIANG
• 金额: $ 22.58万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7151128
• 关键词: Acetylcholine; Adrenergic Agents; Adrenergic Receptor; Age; Aging; Agonist; Area; Arteries; Beds; Blood Circulation; Blood Vessels; Blood flow; Brain; Calcitonin Gene-Related Peptide; Caliber; Cardiovascular Physiology; Cations; Cavia; Cell membrane; Cells; Cellular Membrane; Chemicals; Comparative Study; Condition; Coupling; Disease; Electrophysiology (science); Goals; Hearing; Heterogeneity; In Vitro; Intestines; Ion Channel; Ions; Knowledge; Label; Labyrinth; Measurement; Mediating; Membrane; Membrane Potentials; Mesentery; Metabolic; Methods; Muscle Cells; Muscle Tonus; Nature; Nerve Fibers; Neurons; Neuropeptides; Neurotransmitters; Norepinephrine; Organ; Pharmaceutical Preparations; Physiology; Preparation; Prevention; Property; Purinoceptor; Rate; Receptor Signaling; Relative (related person); Research; Rest; Signal Pathway; Smooth Muscle Myocytes; Spiral Artery of the Endometrium; Sudden Deafness; Techniques; Testing; Trauma; Vascular System; Whole-Cell Recordings; adrenergic; arteriole; cerebral artery; electrical property; hearing impairment; improved; neuromuscular transmission; novel; programs; receptor; research study; response; sound; vascular bed; voltage clamp

Strong evidence suggests that blood circulation disturbances contribute to hearing losses in loud sound- induced trauma, aging, Meni_re's disease, ototoxic drugs and some forms of sudden deafness. To understand and treat these hearing conditions, knowledge of inner ear vascular physiology is a prerequisite. Little is known about the regulating mechanisms of cochlear vessels. The long-term objective of this proposal is to increase our understanding of the cellular and subcellular physiology of these vessels and how they differ from vessels of other vascular beds. Specifically, this proposal aims to: 1) determine the membrane channels and mechanisms that cause two distinct levels of resting potentials in smooth muscle cells of cochlear spiral modiolar artery (SMA); 2) determine the actions of candidate neurotransmitters and neuropeptides on the ion channels, the responsible receptors and the intracellular signaling pathways; 3) identify the nature of neuromuscular transmission in the SMA; 4) determine how the contractile and cellular properties of the SMA differ from small arteries of the brain and intestine. These goals will be achieved by experiments using conventional and whole-cell current- and voltage-clamp recording methods on in vitro smooth muscle cells in segments of the SMA, as well as single-cell labeling and vasotone measurements. Comparative studies of contractile and membrane properties between the SMA and the arterioles from the brain and intestine will be conducted to evaluate the heterogeneity among the vessel beds. With these studies, we expect to describe the unique contractile and membrane properties, key ion- channel features, functional neuromuscular transmitters and related receptors, and mechanisms by which these functioning properties are regulated in the SMA; in addition, we expect to understand how these mechanisms of the SMA differ from those of other vessel beds. The knowledge obtained will improve our understanding of how cochlear blood flow is uniquely regulated, thus contributing to the understanding of circulation-related hearing losses and leading to prevention and treatment of these hearing conditions. The acquired knowledge should also be of significance in broad areas of cardiovascular physiology.

强有力的证据表明，血液循环障碍有助于在响亮的声音听力损失- 诱发性创伤、衰老、Meni_re病、耳毒性药物和某些形式的突发性耳聋。到 了解和治疗这些听力疾病，内耳血管生理学知识是先决条件。 耳蜗血管的调节机制知之甚少。长期目标是 我们的建议是增加我们对这些血管的细胞和亚细胞生理学的理解， 它们不同于其他血管床的血管。 具体来说，这项建议旨在：1）确定引起两种疾病的膜通道和机制 耳蜗螺旋蜗轴动脉（SMA）平滑肌细胞静息电位水平不同; 2） 确定候选神经递质和神经肽对离子通道的作用， 负责受体和细胞内信号通路; 3）确定神经肌肉的性质 4）确定SMA的收缩和细胞特性与SMA的收缩和细胞特性如何不同。 脑和肠的小动脉。这些目标将通过使用常规的 和全细胞电流和电压钳记录方法在体外平滑肌细胞的片段， SMA，以及单细胞标记和血管张力测量。收缩的比较研究 以及SMA与脑和肠的小动脉之间的膜特性 以评价导管床之间的非均质性。 通过这些研究，我们期望描述独特的收缩和膜特性，关键离子- 通道特征，功能性神经肌肉递质和相关受体，以及 这些功能特性在SMA中受到调节;此外，我们希望了解这些特性是如何在SMA中发挥作用的。 SMA的机制不同于其他血管床的机制。获得的知识将提高我们的 了解耳蜗血流是如何独特地调节的，从而有助于理解 循环相关的听力损失，并导致这些听力状况的预防和治疗。的 所获得的知识在心血管生理学的广泛领域中也应该是有意义的。