Myocardial KChIP2 Expression in Guinea Pig Resolves an Expanded Electrophysiologic Role

PloS One
Drew M NassalIsabelle Deschênes

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 prote...Continue Reading

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Citations

Jul 17, 2018·Physiological Reports·Kirstine CalloeJonathan M Cordeiro
May 16, 2018·Cardiovascular Endocrinology & Metabolism·Yang YupingZhou Qing
Sep 25, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Giulia BorghettiMarcello Rota
Dec 5, 2020·Pharmaceutical Patent Analyst·Hermann Am Mucke

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Methods Mentioned

BETA
PCR

Software Mentioned

pClamp
SPSS

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