Abstract
Cardiac ion channels and their respective accessory subunits are critical in maintaining proper electrical activity of the heart. Studies have indicated that the K+ channel interacting protein 2 (KChIP2), originally identified as an auxiliary subunit for the channel Kv4, a component of the transient outward K+ channel (Ito), is a Ca2+ binding protein whose regulatory function does not appear restricted to Kv4 modulation. Indeed, the guinea pig myocardium does not express Kv4, yet we show that it still maintains expression of KChIP2, suggesting roles for KChIP2 beyond this canonical auxiliary interaction with Kv4 to modulate Ito. In this study, we capitalize on the guinea pig as a system for investigating how KChIP2 influences the cardiac action potential, independent of effects otherwise attributed to Ito, given the endogenous absence of the current in this species. By performing whole cell patch clamp recordings on isolated adult guinea pig myocytes, we observe that knock down of KChIP2 significantly prolongs the cardiac action potential. This prolongation was not attributed to compromised repolarizing currents, as IKr and IKs were unchanged, but was the result of enhanced L-type Ca2+ current due to an increase in Cav1.2 protein. In addition, cells with reduced KChIP2 also displayed lowered INa from reduced Nav1.5 protein. Historically, rodent models have been used to investigate the role of KChIP2, where dramatic changes to the primary repolarizing current Ito may mask more subtle effects of KChIP2. Evaluation in the guinea pig where Ito is absent, has unveiled additional functions for KChIP2 beyond its canonical regulation of Ito, which defines KChIP2 as a master regulator of cardiac repolarization and depolarization.
Highlights
K+ channel interacting proteins (KChIPs) represent a class of highly diverse Ca2+-sensors originally discovered for their interaction with the cytoplasmic N-terminus of the Kv4 family of potassium channels [1]
Left ventricular tissue isolated from guinea pig expresses approximately 35-fold less K+ channel interacting protein 2 (KChIP2) than the ventricular tissue from an adult rat (Fig 1B), making the level of KChIP2 mRNA expression comparable to neonatal rat ventricular myocytes
This study sought to characterize the influence of KChIP2 expression in the guinea pig myocardium
Summary
K+ channel interacting proteins (KChIPs) represent a class of highly diverse Ca2+-sensors originally discovered for their interaction with the cytoplasmic N-terminus of the Kv4 family of potassium channels [1]. The assembly of these two proteins creates the native current known as A-type current (IA) in neuronal tissue and the fast-inactivating transient-outward potassium current (Ito,f) in the heart [2,3,4,5,6]. While the expression of Kv4 alone is sufficient to observe this current, co-expression with KChIP results in currents with slowed inactivation, faster recovery.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
