Identification of a specific role for the Na,K-ATPase α2 isoform as a regulator of calcium in the heart
Identification of a specific role for the Na,K-ATPase α2 isoform as a regulator of calcium in the heart
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DOI：
10.1016/s1097-2765(00)80349-4
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发表时间：
1999-05-01
期刊：
影响因子：
16
通讯作者：
Lingrel, JB
中科院分区：
文献类型：
--
作者：
James, PF;Grupp, IL;Lingrel, JB
人们普遍认为，抑制心脏中的Na， k - atp酶，通过影响Na/Ca交换，提高细胞内Ca2+浓度，加强心脏收缩。然而，个体同种异构体对钙调节作用的贡献尚不清楚。对Na、k - atp酶α 1或α 2亚型基因水平降低的小鼠心脏的表型进行评估，清楚地表明这些亚型在体内具有不同的功能作用。杂合子（α 2）心脏在收缩周期中由于钙瞬态增加而过度收缩。相比之下，杂合α - 1型心脏收缩性较弱。这两种异构体的不同功能作用被进一步证明，因为用乌巴因抑制α 2异构体增加了杂合α 1心脏的收缩性。这些结果明确地说明了(α 2na， k - atp酶异构体在心脏收缩期间Ca2+信号传导中的特定作用。
It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous (alpha 2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous alpha 1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the alpha 2 isoform with ouabain increases the contractility of heterozygous alpha 1 hearts. These results definitively illustrate a specific role for the (alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction.