Halothane reduces myofilament Ca2+ sensitivity during muscarinic receptor stimulation of airway smooth muscle.
Halothane reduces myofilament Ca2+ sensitivity during muscarinic receptor stimulation of airway smooth muscle.
复制标题
氟烷可降低气道平滑肌毒蕈碱受体刺激过程中肌丝 Ca2+ 的敏感性。
DOI：
10.1152/ajplung.1996.271.5.l719
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Warner,DO
中科院分区：
文献类型：
--
作者：
Akao,M;Hirasaki,A;Jones,KA;Wong,GY;Bremerich,DH;Warner,DO
本研究使用β-七叶皂苷透化的犬气管平滑肌制备物来检验以下假设：挥发性麻醉剂氟烷通过抑制调节肌丝Ca 2+敏感性的膜受体连接的第二信使系统而不是通过抑制收缩蛋白的Ca（2+）-钙调蛋白激活来降低肌丝Ca 2+敏感性。乙酰胆碱（ACh）引起的GTP依赖性的增加力在恒定的次最大胞质Ca 2+浓度。乙酰胆碱，鸟苷-5 '-O-（3-硫代三磷酸）和蛋白激酶C激动剂12，13-佛波醇二丁酸酯各自显著降低游离Ca 2+的浓度，产生从0.77 +/- 0.09 μ M的半最大响应01、0.19 +/-0.02和0.37 +/- 0.03 μ M，表明肌丝Ca 2+敏感性增加。氟烷（0.92 +/- 0.12 mM）对单独Ca 2+产生的游离Ca 2+浓度-响应曲线没有影响。然而，在存在3 μ M ACh和10 μ M GTP以最大限度地激活毒蕈碱受体的情况下，氟烷显著增加了游离Ca 2+的EC 50，从0.17 +/- 0.01 μ M增加到0.38 +/- 0.03 μ M。这些发现表明，氟烷通过抑制调节肌丝Ca 2+敏感性的膜受体连接的第二信使系统，降低β-七叶皂苷透化犬气管平滑肌中肌丝Ca 2+敏感性。
This study used a beta-escin-permeabilized canine tracheal smooth muscle preparation to test the hypothesis that the volatile anesthetic halothane decreases myofilament Ca2+ sensitivity by inhibiting the membrane receptor-linked second messenger systems that regulate myofilament Ca2+ sensitivity and not by inhibiting Ca(2+)-calmodulin activation of the contractile proteins. Acetylcholine (ACh) caused a GTP-dependent increase in force at constant submaximal cytosolic Ca2+ concentration. ACh, guanosine-5'-O-(3-thiotriphosphate), and the protein kinase C agonist 12,13-phorbol dibutyrate each significantly decreased the concentration of free Ca2+ producing a half-maximal response from 0.77 +/- 0.09 microM (Ca2+ alone) to 0.16 +/- 0.01, 0.19 +/- 0.02, and 0.37 +/- 0.03 microM, respectively, demonstrating an increase in myofilament Ca2+ sensitivity. Halothane (0.92 +/- 0.12 mM) had no effect on the free Ca2+ concentration-response curves generated by Ca2+ alone. However, in the presence of 3 microM ACh plus 10 microM GTP to maximally activate muscarinic receptors, halothane significantly increased the EC50 for free Ca2+ from 0.17 +/- 0.01 microM to 0.38 +/- 0.03 microM. These findings suggest that halothane decreases myofilament Ca2+ sensitivity in beta-escin-permeabilized canine tracheal smooth muscle by inhibiting the membrane receptor-linked second messenger systems that regulate myofilament Ca2+ sensitivity.