CELLULAR MECHANISMS OF CAROTID BODY CHEMOSENSITIVITY

这个项目的目标是量化细胞适应在 在体慢性习服时颈动脉体功能的变化 低氧(刺激高海拔)和慢性低氧与 高碳酸血症(模拟慢性肺部疾病)。颈动脉小体是 低氧呼吸驱动的主要来源，但知之甚少 颈动脉体电生理对慢性适应性的研究 缺氧。膜片钳技术将被用来记录相关电流 分离血管球体细胞的钾、钠、钙离子通道 来自对照组和驯化的大鼠。我们将测试Glomus的变化 与细胞离子通道活性和膜电位相关的 对O2和CO2刺激的适应。确定……的特异性 对颈动脉博格症的测量适应，我们将比较适应 球体细胞对新鲜分离肾上腺变化的反应 嗜铬细胞和培养的PC12细胞暴露于相同的处理。这个 低氧习服对大鼠一氧化氮神经调节的影响 颈动脉体部功能和球体细胞离子通道活性 量化的。我们将确定是否刺激颈动脉小体 谷氨酸起作用，精氨酸和赖氨酸起抑制作用 通过对膜受体的作用或通过直接的物理化学 氨基酸的性质，以及这种调制是否受 低氧适应。我们还将研究细胞内的作用 血管球体细胞钙储存在使用阻滞剂和激动剂的化学接收上 兰尼定和三磷酸肌醇受体治疗前后的变化 适应。这些研究将有助于确定生理学基础 用于健康和疾病中颈动脉体对慢性低氧的适应。

The objective of this project is to quantify the cellular adaptations in carotid body function occurring with in vivo acclimatization to chronic hypoxia (stimulating high altitude) and with combined chronic hypoxia and hypercapnia (simulating chronic lung disease). The carotid body is the primary source of the hypoxic ventilatory drive, but very little is known about the electrophysiological adaptations of the carotid body to chronic hypoxia. Patch clamp techniques will be used to record currents associated with potassium, sodium and calcium ion channels in glomus cells isolated from control and acclimatized rats. We will test for changes in glomus cell ion channel activity and membrane potential associated with acclimatization to O2 and Co2 stimuli. To determine the specificity of measured adaptations to the carotid bogy, we will compare acclimatization responses in glomus cells to change observed in freshly isolated adrenal chromaffin and cultured PC12 cells exposed tot he same treatments. The effects of hypoxic acclimatization on nitric oxide neuromodulation of carotid body function and glomus cell ion channel activity will be quantified. We will determine whether the stimulation of carotid body function by glutamate and inhibition by arginine and lysine is exerted through action on membrane receptors, or through direct physicochemical properties of the amino acids, and whether the modulation is affected by hypoxic acclimatization. We will also study the role of intracellular glomus cell calcium stores on chemoreception using blockers and agonists of ryanodine and inositol triphosphate receptors, before and after acclimatization. These studies will help define the physiological basis for carotid body adaptation to chronic hypoxia in health and disease.