Burt Richard P
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Eur J Pharmacol. 2005 Mar 7;510(1-2):97-105. doi: 10.1016/j.ejphar.2005.01.021.
The possibility that Ca2+ store depletion can stimulate contraction of the rat portal vein was investigated in functional experiments. Ca2+ stores were depleted with phenylephrine or cyclopiazonic acid in the absence of extracellular Ca2+ and then washed out for 30 min. Upon re-addition of extracellular Ca2+, a tonic contraction was produced, showing the stimulus for contraction was Ca2+ store depletion. The contractions were abolished by niflumic acid and nifedipine however, indicating they were dependent on depolarization resulting from opening of Ca2+-activated Cl- channels and Ca2+ influx through voltage-gated channels. Cumulative additions of phenylephrine below 3x10(-6) M did not produce tonic contractions but did in high K+ Krebs solution, where levcromakalim had no effect. This showed the tonic contractions were initially prevented by K+ channel opening. Increased Ca2+ entry through voltage-gated channels may therefore stimulate Ca2+-activated Cl- channels. Ca2+ store depletion could stimulate this by opening store-operated non-selective cation channels, resulting in depolarization.
在功能实验中研究了钙库耗竭刺激大鼠门静脉收缩的可能性。在无细胞外钙的情况下，用去氧肾上腺素或环匹阿尼酸使钙库耗竭，然后洗脱30分钟。重新加入细胞外钙后，产生强直性收缩，表明收缩刺激是钙库耗竭。然而，尼氟灭酸和硝苯地平可消除这些收缩，表明它们依赖于钙激活氯离子通道开放和通过电压门控通道的钙内流所导致的去极化。低于3×10⁻⁶ M的去氧肾上腺素累积添加不会产生强直性收缩，但在高钾 Krebs 溶液中会产生，在该溶液中左卡尼汀无作用。这表明强直性收缩最初被钾通道开放所阻止。因此，通过电压门控通道增加的钙内流可能刺激钙激活氯离子通道。钙库耗竭可通过打开储存操纵性非选择性阳离子通道来刺激这一过程，导致去极化。
