K+ depolarization induces RhoA kinase translocation to caveolae and Ca2+ sensitization of arterial muscle.
K+ depolarization induces RhoA kinase translocation to caveolae and Ca2+ sensitization of arterial muscle.
复制标题
K 去极化诱导 RhoA 激酶易位至小凹，并导致动脉肌肉 Ca2+ 敏化。
DOI：
10.1152/ajpcell.00501.2002
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Ratz,PaulH
中科院分区：
文献类型：
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作者：
Urban,NicoleH;Berg,KrystinaM;Ratz,PaulH
KCl通过升高细胞内游离Ca 2+引起平滑肌收缩，而受体刺激激活另一种机制，称为Ca 2+敏化，其可能涉及RhoA相关激酶（ROK）和PKC的激活。然而，最近的研究支持KCl也可能增加Ca 2+敏感性的假设。我们的数据表明，PKC抑制剂GF-109203 X没有，而ROK抑制剂Y-27632，抑制KCl诱导的强直（5分钟）力和肌球蛋白轻链（MLC）磷酸化在兔动脉。Y-27632还抑制BAY K 8644和离子霉素诱导的MLC磷酸化和力，但不抑制KCl诱导的Ca 2+内流或峰值（15 s）力。此外，KCl和BAY K 8644在30秒时使共定位于小窝的ROK量几乎增加了一倍，这一时间早于Y-27632对力的抑制。共定位不受Y-27632的抑制，但被硝苯地平和钙调蛋白阻滞剂三氟拉嗪所消除。这些数据支持KCl通过ROK激活引起Ca 2+敏化的假设。我们讨论了一种新的模型，涉及易位到小窝，是依赖于Ca 2+的进入，涉及Ca 2 +-钙调蛋白激活的韩国激活。
KCl causes smooth muscle contraction by elevating intracellular free Ca2+, whereas receptor stimulation activates an additional mechanism, termed Ca2+sensitization, that can involve activation of RhoA-associated kinase (ROK) and PKC. However, recent studies support the hypothesis that KCl may also increase Ca2+sensitivity. Our data showed that the PKC inhibitor GF-109203X did not, whereas the ROK inhibitor Y-27632 did, inhibit KCl-induced tonic (5 min) force and myosin light chain (MLC) phosphorylation in rabbit artery. Y-27632 also inhibited BAY K 8644- and ionomycin-induced MLC phosphorylation and force but did not inhibit KCl-induced Ca2+entry or peak (∼15 s) force. Moreover, KCl and BAY K 8644 nearly doubled the amount of ROK colocalized to caveolae at 30 s, a time that preceded inhibition of force by Y-27632. Colocalization was not inhibited by Y-27632 but was abolished by nifedipine and the calmodulin blocker trifluoperazine. These data support the hypothesis that KCl caused Ca2+sensitization via ROK activation. We discuss a novel model for ROK activation involving translocation to caveolae that is dependent on Ca2+entry and involves Ca2+-calmodulin activation.