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Contribution of KChIP2 to the developmental increase in transient outward current of rat cardiomyocytes.

Authors: Kobayashi, T  Yamada, Y  Nagashima, M  Seki, S  Tsutsuura, M  Ito, Y  Sakuma, I  Hamada, H  Abe, T  Tohse, N 
Citation: Kobayashi T, etal., J Mol Cell Cardiol. 2003 Sep;35(9):1073-82.
Pubmed: (View Article at PubMed) PMID:12967630

The Ca(2+)-independent, voltage-gated transient outward current (I(to)) displays a marked increase during development of cardiomyocytes. However, the molecular mechanism remained unclear. In rat adult ventricular myocytes, I(to) can be divided into a fast (I(to,f)) and a slow (I(to,s)) component by recovery process from inactivation. Voltage-gated K(+) channel-interacting proteins 2 (KChIP2) has recently been shown to modify membrane expressions and current densities of I(to,f). Here we examined the developmental change of I(to) and the putative molecular correlates of I(to,f) (Kv4.2 and Kv4.3) and KChIP2 in rat ventricular myocytes. Even in rat embryonic day 12 (E12) myocytes, we detected I(to). However, I(to) in E12 was solely composed of I(to,s). In postnatal day 10 (P10), we recorded much increased I(to) composed of two components (I(to,f) and I(to,s)), and I(to,f) was dominant. Thus, the developmental increase of I(to) from E12 to P10 can be explained by the dramatic appearance of I(to,f). Real-time RT-PCR revealed that Kv4.2 and Kv4.3 mRNA levels were slightly changed. By contrast, KChIP2 mRNA level increased from E12 to P10 by 731-fold. Therefore, the huge increase of KChIP2 expression was likely to be the cause of the great increase of I(to,f). In order to confirm that KChIP2 is crucial to induce I(to,f), we used adenoviral gene transfer technique. When KChIP2 was over-expressed in E12 myocytes, a great amplitude of I(to,f) appeared. Immunocytochemical experiments also demonstrated that KChIP2 enhanced the trafficking of Kv4.2 channels to cell surface. These results indicate that KChIP2 plays an important role in the generation of functional I(to,f) channels during development.

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CRRD Object Information
CRRD ID: 7207200
Created: 2013-01-23
Species: All species
Last Modified: 2013-01-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.