Tabo M, Ohta T, Ito S, Nakazato Y
Laboratory of Pharmacology, School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Eur J Pharmacol. 1996 Oct 10;313(1-2):151-8. doi: 10.1016/0014-2999(96)00517-1.
The effects of K+ on Ca2+ influx after transient depletion of Ca2+ stores with carbachol and long-lasting depletion with thapsigarin or ryanodine were examined in fura-2-loaded rat ileal smooth muscle. After transient depletion of Ca2+ stores, application of Ca2+ caused a rise in [Ca2+]i and a contraction, both of which were increased with increasing K+ applied simultaneously in the absence of methoxyverapamil, but were decreased in its presence. In tissues, long-lasting depletion of Ca2+ stores treated with thapsigarin or ryanodine, [Ca2+]i and tension were dose dependently increased by the application of Ca2+ regardless of the absence or presence of methoxyverapamil. These responses were inhibited by K+ replacement of Na+ in a dose-dependent manner and the inhibitory action of K+ was attenuated by increasing extracellular Ca2+. The influx of Mn2+ was much greater in the tissues pretreated with thapsigarin or ryanodine than in untreated tissues. The enhanced Mn2+ influx was inhibited by the replacement of Na+ with K+. These results provide further evidence for the presence of a Ca2+ entry mechanism evoked by the depletion of Ca2+ stores in rat ileal smooth muscle, and suggest that there are two types of Ca2+ entry pathways to refill Ca2+ stores, one sensitive and the other insensitive to Ca2+ channel blockers. Ca2+ entry through the latter pathway is inhibited by increasing external K+, perhaps due to a reduction of the electrochemical gradient for Ca2+ across the plasma membrane.
在负载fura - 2的大鼠回肠平滑肌中，研究了用卡巴胆碱短暂耗尽Ca2+储存以及用毒胡萝卜素或雷诺丁长期耗尽Ca2+储存后，K+对Ca2+内流的影响。在Ca2+储存短暂耗尽后，施加Ca2+会导致[Ca2+]i升高和收缩，在不存在甲氧维拉帕米的情况下，随着同时施加的K+浓度增加，这两者都会增强，但在其存在时则会减弱。在用毒胡萝卜素或雷诺丁处理使Ca2+储存长期耗尽的组织中，无论是否存在甲氧维拉帕米，施加Ca2+都会使[Ca2+]i和张力呈剂量依赖性增加。这些反应可被K+取代Na+以剂量依赖性方式抑制，并且K+的抑制作用会因细胞外Ca2+浓度增加而减弱。在用毒胡萝卜素或雷诺丁预处理的组织中，Mn2+的内流比未处理的组织大得多。用K+取代Na+可抑制增强的Mn2+内流。这些结果为大鼠回肠平滑肌中Ca2+储存耗尽诱发的Ca2+进入机制的存在提供了进一步证据，并表明存在两种补充Ca2+储存的Ca2+进入途径，一种对Ca2+通道阻滞剂敏感，另一种不敏感。通过后一种途径的Ca2+进入会因外部K+增加而受到抑制，这可能是由于跨质膜的Ca2+电化学梯度降低所致。
