Effects of hypoxia and dithionite on catecholamine release from isolated type I cells of the rat carotid body
Effects of hypoxia and dithionite on catecholamine release from isolated type I cells of the rat carotid body
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DOI：
10.1111/j.1469-7793.2000.00719.x
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发表时间：
2000-03-15
影响因子：
5.5
通讯作者：
Peers, C
中科院分区：
文献类型：
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作者：
Carpenter, E;Hatton, CJ;Peers, C
1.采用电流记录法研究了缺氧和缺氧对大鼠颈动脉体I型细胞分泌儿茶酚胺的影响.当细胞在室温（21-24 ℃）或35-37 ℃灌注时，无论使用Hepes缓冲液还是HCO（3）（-）/CO（2）缓冲液，缺氧（P（O2）8-14 mmHg）始终不能引起I型细胞分泌儿茶酚胺。升高细胞外[K（+）]引起浓度依赖性的I型细胞分泌，其阈值浓度约为25 mM。在此水平的细胞外K（+）存在下，缺氧（P（O2）8-14 mmHg）引起分泌的显著增强，其被200 μ M Cd（2+）完全阻断，Cd（2+）是电压门控Ca（2+）通道的非特异性阻断剂。当细胞外[K（+）]为5 mM时，缺氧（含0.5 mM连二亚硫酸盐的N（2）平衡溶液）诱发I型细胞的胞吐作用。这种分泌可被细胞外Ca（2+）的去除完全抑制，但不受Cd（2+）（200 μ M）、Ni（2+）（2 mM）、Zn（2+）（1 mM）或硝苯地平（2 μ M）的显著影响。当将0.5mM连二亚硫酸盐加入到空气平衡的溶液中时，也观察到分泌。缺氧也诱发化学感受性嗜铬细胞瘤（PC 12）细胞的分泌，其完全依赖于Ca（2+），但不受Cd（2+）（200 μ M）的影响。我们的研究结果表明，缺氧可以引起分离的I型细胞分泌儿茶酚胺，但只有在存在升高的细胞外[K（+）]。这可能是由于细胞在解离后相对超极化。此外，我们已经表明，连二亚硫酸盐引起儿茶酚胺释放，而不管POP水平，这种释放主要是由于一个人工Ca（2+）内流途径激活连二亚硫酸盐的存在。
1. Amperometric recordings were conducted to investigate the ability of hypoxia and anoxia to evoke quantal catecholamine secretion from isolated type I cells of the rat carotid body.2. Hypoxia (P(O2) 8-14 mmHg) consistently failed to evoke catecholamine secretion from type I cells, when cells were perfused either at room temperature (21-24 degrees C) or at 35-37 degrees C, and regardless of whether Hepes- or HCO(3)(-)/CO(2)-buffered solutions were used.3. Elevating extracellular [K(+)] caused concentration-dependent secretion from individual type I cells, with a threshold concentration of approximately 25 mM. In the presence of this level of extracellular K(+), hypoxia (P(O2) 8-14 mmHg) caused a marked enhancement of secretion which was fully blocked by 200 mu M Cd(2+), a non-specific blocker of voltage-gated Ca(2+) channels.4. Anoxia (N(2)-equilibrated solution containing 0.5 mM dithionite) evoked exocytosis from type I cells when extracellular [K(+)] was 5 mM. This secretion was completely inhibited by removal of extracellular Ca(2+), but was not significantly affected by Cd(2+) (200 mu M), Ni(2+) (2 mM), Zn(2+) (1 mM) or nifedipine (2 mu M). Secretion was also observed when 0.5 mM dithionite was added to air-equilibrated solutions.5. Anoxia also evoked secretion from chemoreceptive phaeochromocytoma (PC12) cells, which was wholly Ca(2+) dependent, but unaffected by Cd(2+) (200 mu M).6. Our results suggest that hypoxia can evoke catecholamine secretion from isolated type I cells, but only in the presence of elevated extracellular [K(+)]. This may be due to the cells being relatively hyperpolarized following dissociation. In addition, we have shown that dithionite evokes catecholamine release regardless of POP levels, and this release is due mainly to an artefactual Ca(2+) influx pathway activated in the presence of dithionite.