Abstract
Electrophysiological remodeling of cardiac potassium ion channels is important in the progression of heart failure. A reduction of the transient outward potassium current (Ito) in mammalian heart failure is consistent with a reduced expression of potassium channel interacting protein 2 (KChIP2, a KV4 subunit). Approaches have been made to investigate the role of KChIP2 in shaping cardiac Ito, including the use of transgenic KChIP2 deficient mice and viral overexpression of KChIP2. The interplay between Ito and myocardial calcium handling is pivotal in the development of heart failure, and is further strengthened by the dual role of KChIP2 as a functional subunit on both KV4 and CaV1.2. Moreover, the potential arrhythmogenic consequence of reduced Ito may contribute to the high relative incidence of sudden death in the early phases of human heart failure. With this review, we offer an overview of the insights into the physiological and pathological roles of KChIP2 and we discuss the limitations of translating the molecular basis of electrophysiological remodeling from animal models of heart failure to the clinical setting.
Highlights
The normal pumping action of the mammalian heart is critically dependent on the cardiac electrophysiological function
Frontiers in Physiology | Cardiac Electrophysiology transmembrane action potentials were comparable in ventricular multicellular preparations from KChIP2−/− and WT control mice paced at 2 Hz (Thomsen et al, 2009c), which was presumably secondary to an upregulation of a 4-aminopyridine-sensitive current that restored peak outward potassium current density in KChIP2−/− mice (Figure 1)
SUMMARY AND CONCLUDING REMARKS Substantial progress has been made in the mapping of the multiple characteristics and roles of KChIP2 in the heart
Summary
The normal pumping action of the mammalian heart is critically dependent on the cardiac electrophysiological function. A reduction of the transient outward potassium current (Ito) in mammalian heart failure is consistent with a reduced expression of potassium channel interacting protein 2 (KChIP2, a KV4 subunit).
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