新生大鼠颈动脉体细胞在慢性体内缺氧后的钠电流和钾电流

Sodium and potassium current in neonatal rat carotid body cells following chronic in vivo hypoxia.

作者信息

Hempleman S C

机构信息

Department of Medicine, University of California at San Diego, La Jolla 92093-0623, USA.

出版信息

Brain Res. 1995 Nov 13;699(1):42-50. doi: 10.1016/0006-8993(95)00850-p.

DOI:10.1016/0006-8993(95)00850-p

PMID:8616612

Abstract

Chronic hypoxic acclimatization modifies ventilatory reflexes arising from carotid body stimulation. To explore this, the effects of in vivo chronic hypoxia on membrane currents were quantified in chemoreceptive carotid body glomus cells. Pregnant rats were maintained in either normoxia (NORM: inspired oxygen tension 141 mmHg), or hypoxia (CHX: inspired oxygen tension 80 mmHg) from day 3 of gestation, to day 5-10 postpartum. Whole cell patch clamp recordings were then made from the mechanically and enzymatically dissociated carotid body glomus cells of the rat pups (NORM: 41 cells, CHX: 36 cells) and comparisons of means +/- S.E.M. were made with unpaired t-tests. Glomus cells were bright under phase contrast illumination, formed clusters, were histochemically positive for catecholamines and possessed voltage-gated potassium currents that were depressed by acute hypoxia. Acclimatization to chronic hypoxia did not affect rat pup whole body mass (CHX: 12.0 +/- 0.7 g vs. NORM: 11.0 +/- 0.2 g), but it significantly increased blood hematocrit (CHX: 48.7 +/- 0.9% vs. NORM: 37.8 +/- 0.5%, P < 0.05). Sodium current was not uniformly present in glomus cells from either group, but sodium current was observed in a greater proportion of glomus cells isolated from the chronically hypoxic pups (CHX: 72% vs. NORM: 46%, P < 0.05). The mean peak tetrodotoxin-sensitive sodium current evoked by -70 mV to +10 mV depolarizations was greater after hypoxic acclimatization (CHX: -100 +/- 25 pA vs. NORM: -38 +/- 15 pA, P < 0.05), but the sodium current density (pA/pF) was unchanged. In contrast, the mean peak voltage-gated potassium current (pA) evoked by -70 mV to 0 mV depolarizations was unchanged by acclimatization, but the potassium current density (pA/pF) was reduced (P < 0.05). Unchanged sodium current density coupled with decreased potassium current density may make glomus cells more excitable during exposure to chronic in vivo hypoxia.

摘要

慢性低氧适应会改变由颈动脉体刺激引发的通气反射。为探究这一点，对化学感受性颈动脉体球细胞中体内慢性低氧对膜电流的影响进行了量化。从妊娠第3天至产后第5 - 10天，将妊娠大鼠饲养于常氧环境（NORM：吸入氧分压141 mmHg）或低氧环境（CHX：吸入氧分压80 mmHg）。随后对大鼠幼崽经机械和酶解分离得到的颈动脉体球细胞进行全细胞膜片钳记录（NORM组：41个细胞，CHX组：36个细胞），并采用非配对t检验对均值±标准误进行比较。球细胞在相差显微镜下明亮，形成簇状，儿茶酚胺组织化学染色呈阳性，且具有电压门控钾电流，该电流可被急性低氧抑制。慢性低氧适应对大鼠幼崽的全身质量无影响（CHX组：12.0±0.7 g vs. NORM组：11.0±0.2 g），但显著增加了血液红细胞压积（CHX组：48.7±0.9% vs. NORM组：37.8±0.5%，P < 0.05）。两组球细胞中钠电流并非均一存在，但在从慢性低氧幼崽分离得到的球细胞中观察到钠电流的比例更高（CHX组：72% vs. NORM组：46%，P < 0.05）。经低氧适应后，由 - 70 mV至 + 10 mV去极化诱发的平均峰值河豚毒素敏感钠电流更大（CHX组： - 100±25 pA vs. NORM组： - 38±15 pA，P < 0.05），但钠电流密度（pA/pF）未改变。相比之下，由 - 70 mV至0 mV去极化诱发的平均峰值电压门控钾电流（pA）经适应后未改变，但钾电流密度（pA/pF）降低（P < 0.05）。钠电流密度不变而钾电流密度降低可能使球细胞在暴露于体内慢性低氧期间更易兴奋。