RELATIONSHIP BETWEEN KCHIP2 AND TRANSIENT OUTWARD CURRENT OF DEVELOPING RAT HEART

摘要

In rat ventricular myocytes, Ca~(2+)-independent, voltage-gated transient outward current (I_(to)) is composed of two components, I_(to,f) and I_(to,s), which are distinguished by the rate of recovery from inactivation. The I_(to) in embryonic day 12 (E12) myocytes was solely composed of I_(to,s), and the I_(to) in postnatal day 10 (P10) myocytes was mainly composed of I_(to,f). These results implied that the increasing component of I_(to) from E12 to P10 was only I_(to,f). However, real-time RT-PCR revealed that Kv4.2 and 4.3 mRNA levels were almost unchanged. Recently, voltage-gated K+ channel-interacting proteins 2 (KChIP2) has been shown to modify membrane expressions and current densities of 7tof. Therefore, we evaluated the relationship between KChIP2 and I_(to,f) during development. By contrast with Kv4.2/4.3, KChIP2 mRNA level was extremely increased from E12 to P10 by 731 folds. When KChIP2 was over-expressed in E12 myocytes by use of adenoviral gene transfer technique, the I_(to,f) in a great amplitude appeared. Immunocytochemical study demonstrated that KCHP2 enhanced the trafficking of Kv4.2 channels to cell surface. The present results indicate that KChIP2 is responsible for the appearance of I_(to,f) with cardiac development.