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二磺酸芪阴离子通道阻滞剂对豚鼠心肌的作用。

Effect of disulfonic stilbene anion-channel blockers on the guinea-pig myocardium.

作者信息

Minocherhomjee A M, Roufogalis B D, McNeill J H

出版信息

Can J Physiol Pharmacol. 1985 Aug;63(8):912-7. doi: 10.1139/y85-151.

DOI:10.1139/y85-151
PMID:4075266
Abstract

The role of anions in the maintenance of tension in electrically driven left atria isolated from guinea pigs has been examined. The disulfonic stilbene anion-channel blockers SITS (4-acetamido-4'-isothiocyanostilbene 2'-disulfonate) and DIDS (4,4'-diisothiocyano-2,2'-stilbene disulfonate) decreased the contractile force developed in a time- and concentration-dependent manner. As in the red cell anion channel, DIDS was more potent than SITS, but the maximal inhibition of tension produced by N-(4-azido-2-nitrophenyl)-2-aminoethyl sulfonate (NAP-taurine) was considerably lower than the near maximal inhibition produced by SITS and DIDS. The inhibition by SITS and DIDS was irreversible, suggesting a covalent interaction, and could not be overcome by increasing the calcium concentration or the frequency of stimulation. Consistent with a requirement for chloride anion, substitution of chloride and bicarbonate by the impermeant anion gluconate did not support contraction, while only partial tension was maintained with the lipophilic anions acetate and thiocyanate. Incubation of atria with 400 microM SITS blocked both 36Cl and 45Ca uptake to a similar extent, whereas the efflux of both these ions was not affected by incubation of the atria with SITS. The blockade by disulfonic stilbene anion-channel blockers of the contraction of the guinea pig myocardium may result from impairment of excitation-contraction coupling.

摘要

研究了阴离子在维持从豚鼠分离的电驱动左心房张力中的作用。二磺酸芪阴离子通道阻滞剂SITS(4-乙酰氨基-4'-异硫氰酸芪2'-二磺酸盐)和DIDS(4,4'-二异硫氰酸-2,2'-芪二磺酸盐)以时间和浓度依赖性方式降低了产生的收缩力。与红细胞阴离子通道一样,DIDS比SITS更有效,但N-(4-叠氮基-2-硝基苯基)-2-氨基乙磺酸盐(NAP-牛磺酸)对张力的最大抑制作用明显低于SITS和DIDS产生的近乎最大抑制作用。SITS和DIDS的抑制作用是不可逆的,表明存在共价相互作用,并且不能通过增加钙浓度或刺激频率来克服。与对氯离子的需求一致,用不可渗透的阴离子葡萄糖酸盐替代氯离子和碳酸氢盐不能支持收缩,而用亲脂性阴离子乙酸盐和硫氰酸盐仅维持部分张力。用400 microM SITS孵育心房对36Cl和45Ca的摄取阻断程度相似,而这些离子的流出不受用SITS孵育心房的影响。二磺酸芪阴离子通道阻滞剂对豚鼠心肌收缩的阻断可能是由于兴奋-收缩偶联受损所致。

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