Differential effects of hypoxia on the intracellular Ca2+ concentration of myocytes isolated from different regions of the rat pulmonary arterial tree
Differential effects of hypoxia on the intracellular Ca2+ concentration of myocytes isolated from different regions of the rat pulmonary arterial tree
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DOI：
10.1113/expphysiol.1998.sp004117
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发表时间：
1998-05-01
影响因子：
2.7
通讯作者：
Kozlowski, RZ
中科院分区：
文献类型：
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作者：
Bakhramov, A;Evans, AM;Kozlowski, RZ
缺氧肺血管收缩（HPV）可能介导，部分是由肺动脉平滑肌固有的氧感应机制。有人提出，缺氧抑制K+电导，从而促进膜去极化，随后激活l型Ca2+通道，最终收缩。我们监测了缺氧诱导的细胞内Ca2+浓度（[Ca2+](1)）的变化，从大鼠肺动脉树分离的单个肌细胞使用显微荧光法和比例测量的吲哚-1荧光。[Ca2+](1)的基础水平在35-80 nM范围内，细胞在休息时处于静止状态，没有自发的[Ca2+]振荡(1)。当细胞外K+浓度（[K+](o)）增加到20 mM时，[Ca2+](1)从60 nM左右增加到100 nM左右。这种增加被硝苯地平消除，证明存在，并且需要激活，功能性电压门控的l型Ca2+通道。缺氧（P-O2 $ 30 mmHg；贯穿）对肺内主动脉或其一、二、三分支分离的肌细胞的静息[Ca2+](1)几乎没有影响。然而，当通过增加[K+](0)至20 mM来提高[Ca2+](1)时，在从主导管和肺内动脉初级分支分离的细胞中，发现缺氧使[Ca2+](1)从类似于110 nM降低到类似于70 nM。与此形成鲜明对比的是，当[Ca2+](i)升高时，通过将[K+](o)增加到20 mM，在肺内动脉二级和三级分支分离的肌细胞中，缺氧诱导[Ca2+](i)进一步可逆增加，从类似于160到类似于240 nM。在硝苯地平存在的情况下，无论是单独缺氧还是联合20 mM K+，都不会引起[Ca2+](i)的增加。我们得出结论，缺氧可能会调节[Ca2+](i)在大鼠肺动脉肌细胞只有在其升高后，去极化刺激。
Hypoxic pulmonary vasoconstriction (HPV) may be mediated, in part, by an oxygen-sensing mechanism intrinsic to pulmonary arterial smooth muscle. It has been proposed that hypoxia inhibits a K+ conductance, which promotes membrane depolarization, subsequent activation of L-type Ca2+ channels and ultimately constriction. We have monitored hypoxia-induced changes in the intracellular Ca2+ concentration ([Ca2+](1)) of single myocytes isolated from the rat pulmonary arterial tree using microspectrofluorimetry and ratiometric measurement of indo-1 fluorescence. The basal level of [Ca2+](1) was in the range 35-80 nM and cells were quiescent at rest exhibiting no spontaneous oscillations in [Ca2+](1). When the extracellular K+ concentration ([K+](o)) was raised to 20 mM, the [Ca2+](1) increased from similar to 60 to similar to 100 nM. This increase was abolished by nifedipine, demonstrating the presence, and need for activation, of functional voltage-gated L-type Ca2+ channels. Hypoxia (P-O2 $ 30 mmHg; throughout) had little effect on the resting [Ca2+](1) in myocytes isolated from either the main intrapulmonary artery, or its primary, secondary or tertiary branches. However, upon raising the [Ca2+](1) by increasing [K+](o) to 20 mM, hypoxia was found to lower [Ca2+](1), from similar to 110 to similar to 70 nM, in cells isolated from the main conduit and primary branches of the intrapulmonary artery. In marked contrast, when [Ca2+](i) was raised, by increasing [K+](o) to 20 mM, in myocytes isolated from secondary and tertiary branches of the intrapulmonary artery, hypoxia induced a further reversible increase in the [Ca2+](i) from similar to 160 to similar to 240 nM. Neither hypoxia alone nor in combination with 20 mM K+, induced any increase in the [Ca2+](i) in the presence of nifedipine. We conclude that hypoxia may modulate [Ca2+](i) in rat pulmonary artery myocytes only following its elevation by a depolarizing stimulus.