Chloride ion currents contribute functionally to norepinephrine-induced vascular contraction
Chloride ion currents contribute functionally to norepinephrine-induced vascular contraction
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DOI：
10.1152/ajpheart.1998.275.1.h151
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发表时间：
1998-07-01
影响因子：
4.8
通讯作者：
Barna, TJ
中科院分区：
文献类型：
--
作者：
Lamb, FS;Barna, TJ
去甲肾上腺素（NE）增加血管平滑肌（VSM）细胞的Cl-外排。氯离子电导的增加产生膜去极化。我们假设，如果Cl-电流对激动剂诱导的去极化很重要，那么干扰细胞Cl-处理应该会改变收缩性。在碳酸氢盐缓冲液中研究了大鼠主动脉环的等距收缩。用130毫米甲磺酸盐（MS； 8毫米Cl-）取代细胞外Cl-不会引起收缩。在这种低cl缓冲液中，NE和5 -羟色胺诱导的收缩增强，而在没有Ca2+的情况下，对K+、BAY K 8644或NE的反应没有改变。用I或br抑制对NE的反应取代Cl-。布美他尼（10(-5)M）或无碳酸氢盐（10 mM HEPES）条件下抑制Cl-转运抑制NE-但不抑制kcl诱导的收缩。Cl-通道阻滞剂DIDS （10(-3) M）、蒽-9-羧酸（10(-3)M）和尼氟酸（10（-5)M）均能抑制ne诱导的收缩，而他莫昔芬（10-5）M）则没有。最后，环吡唑酸（10(-7)M）或瑞诺定（10(-5)M）对肌浆网状功能的破坏阻止了低cl -缓冲液对NE产生的峰响应的增加。我们得出结论，通透性序列为I- > Br- > Cl- > MS的Cl-电流对激动剂诱导的VSM收缩至关重要。
Norepinephrine (NE) increases Cl- efflux from vascular smooth muscle (VSM) cells. An increase in Cl- conductance produces membrane depolarization. We hypothesized that if Cl- currents are important for agonist-induced depolarization, then interfering with cellular Cl- handling should alter contractility. Isometric contraction of rat aortic rings was studied in a bicarbonate buffer. Substitution of extracellular Cl- with 130 mM methanesulfonate (MS; 8 mM Cl-) did not cause contraction. NE- and serotonin-induced contractions were potentiated in this low-Cl- buffer, whereas responses to K+, BAY K 8644, or NE in the absence of Ca2+ were unaltered. Substitution of Cl- with I- or Br-suppressed responses to NE. Inhibition of Cl- transport with bumetanide (10(-5) M) or bicarbonate-free conditions (10 mM HEPES) inhibited NE- but not KCl-induced contraction. The Cl--channel blockers DIDS (10(-3) M), anthracene-9-carboxylic acid (10(-3) M), and niflumic acid (10(-5) M) all inhibited NE-induced contraction, whereas tamoxifen (10-5 M) did not. Finally, disruption of sarcoplasmic reticular function with cyclopiazonic acid (10(-7) M) or ryanodine (10(-5) M) prevented the increase in the peak response to NE produced by low-Cl- buffer. We conclude that a Cl- current with a permeability sequence of I- > Br- > Cl- > MS is critical to agonist-induced contraction of VSM.