CELLULAR MECHANISMS OF CAROTID BODY CHEMOSENSITIVITY

这个项目的目标是量化细胞的适应性， 颈动脉体功能发生与体内适应慢性 缺氧（刺激高海拔）和慢性缺氧和 高碳酸血症（模拟慢性肺病）。 颈动脉体是 缺氧性脑脊髓炎的主要来源，但知之甚少 关于颈动脉体对慢性 缺氧 膜片钳技术将用于记录相关的电流 与分离的血管球细胞中的钾、钠和钙离子通道 从对照组和驯化的大鼠。 我们会检测血管球的变化 细胞离子通道活性和膜电位 适应O2和CO2刺激。 确定的特异性 测量适应颈动脉bogy，我们将比较适应 血管球细胞对新鲜分离的肾上腺中观察到的变化的反应 嗜铬细胞和培养的PC 12细胞暴露于相同的处理。 的 低氧习服对一氧化氮神经调节作用的影响 颈动脉体功能和血管球细胞离子通道活性 量化。 我们将确定是否刺激颈动脉体 谷氨酸的功能和精氨酸和赖氨酸的抑制作用 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，以及调节是否受 低氧习服 我们还将研究细胞内 血管球细胞钙储存对化学感受的影响 兰尼碱和三磷酸肌醇受体，治疗前后 驯化 这些研究将有助于确定 用于颈动脉体适应健康和疾病中的慢性缺氧。

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.