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删除辅助亚基KChIP2会导致I(to,f)丧失，并增加I(K,slow)，从而维持正常的动作电位构型。

Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration.

作者信息

Thomsen Morten B, Sosunov Eugene A, Anyukhovsky Evgeny P, Ozgen Nazira, Boyden Penelope A, Rosen Michael R

机构信息

Danish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark.

出版信息

Heart Rhythm. 2009 Mar;6(3):370-7. doi: 10.1016/j.hrthm.2008.11.023. Epub 2008 Nov 27.

DOI:10.1016/j.hrthm.2008.11.023
PMID:19251214
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2731656/
Abstract

BACKGROUND

Four voltage-gated potassium currents, I(to,f) (K(V)4.2), I(to,s) (K(V)1.4), I(K,slow) (K(V)1.5+K(V)2.1), and I(SS) (TASK1), govern murine ventricular repolarization. Although the accessory subunit KChIP2 influences I(to,f) expression, in preliminary experiments we found that action potential duration (APD) is maintained in KChIP2 knockout mice.

OBJECTIVE

We tested the role of KChIP2 in regulating APD and studied the underlying ionic currents.

METHODS

We used microelectrode techniques, whole-cell patch clamp studies, and real-time polymerase chain reaction amplification to characterize ventricular repolarization and its determinants in wild-type and KChIP2(-/-) mice.

RESULTS

Despite comparable baseline action potentials, APD was more markedly prolonged by 4-aminopyridine (4-AP) in KChIP2(-/-) preparations. Peak K(+) current densities were similar in wild-type and KChIP2(-/-) cells (mean +/- SEM I(P): 28.3 +/- 2 (n = 27) vs. 29.2 +/- 2 pA/pF (n = 24), respectively; P > .05). Heteropodatoxin-2 (HpTx-2, 1 microM) had no effect on current amplitude in KChIP2(-/-) myocytes. The current fractions sensitive to 4-AP (50 microM and 1 mM) were larger in KChIP2(-/-) than wild-type (P < .05). Real-time polymerase chain reaction showed absence of KChIP2 and increased K(V)1.5 expression in KChIP2(-/-) ventricular myocardium.

CONCLUSION

KChIP2 deficiency eliminated HpTx-2-sensitive I(to,f), but had little impact on total APD, secondary to upregulation of 4-AP-sensitive I(K,slow) in association with increased K(V)1.5 expression. There is increased sensitivity to 4-AP-mediated APD prolongation in KChIP2(-/-). Thus, KChIP2 seems important for murine repolarization in circumstances of reduced repolarization reserve.

摘要

背景

四种电压门控钾电流，即I(to,f)（K(V)4.2）、I(to,s)（K(V)1.4）、I(K,slow)（K(V)1.5 + K(V)2.1）和I(SS)（TASK1），控制着小鼠心室复极化。尽管辅助亚基KChIP2影响I(to,f)的表达，但在初步实验中我们发现KChIP2基因敲除小鼠的动作电位时程（APD）得以维持。

目的

我们测试了KChIP2在调节APD中的作用，并研究了其潜在的离子电流。

方法

我们使用微电极技术、全细胞膜片钳研究和实时聚合酶链反应扩增来表征野生型和KChIP2(-/-)小鼠的心室复极化及其决定因素。

结果

尽管基线动作电位相当，但在KChIP2(-/-)标本中，4-氨基吡啶（4-AP）更显著地延长了APD。野生型和KChIP2(-/-)细胞中的峰值K(+)电流密度相似（平均±标准误I(P)：分别为28.3±2（n = 27）和29.2±2 pA/pF（n = 24）；P>.05）。异足毒素-2（HpTx-2，1 microM）对KChIP2(-/-)心肌细胞的电流幅度没有影响。对4-AP（50 microM和1 mM）敏感的电流分数在KChIP2(-/-)中比野生型更大（P<.05）。实时聚合酶链反应显示KChIP2(-/-)心室心肌中不存在KChIP2且K(V)1.5表达增加。

结论

KChIP2缺乏消除了对HpTx-2敏感的I(to,f)，但对总APD影响不大，这是由于与K(V)1.5表达增加相关的对4-AP敏感的I(K,slow)上调所致。KChIP2(-/-)对4-AP介导的APD延长更敏感。因此，在复极化储备减少的情况下，KChIP2似乎对小鼠复极化很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/ab0e89850d39/nihms119361f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/49c6437d5d85/nihms119361f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/5a23e3b9813b/nihms119361f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/79c685ce8bd3/nihms119361f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/9b673519000f/nihms119361f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/0a2bf91c3a84/nihms119361f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/ab0e89850d39/nihms119361f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/49c6437d5d85/nihms119361f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/5a23e3b9813b/nihms119361f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/79c685ce8bd3/nihms119361f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/9b673519000f/nihms119361f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/0a2bf91c3a84/nihms119361f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/2731656/ab0e89850d39/nihms119361f6.jpg

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