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Kv channel-interacting protein 2
Compelling evidence from transgenic mice, immunoprecipitation data, gene expression analyses and functional heterologous expression studies supports the role of Kv channel interacting proteins (KChIPs) as modulators of Kv4 channels underlying the cardiac transient outward current and neuronal A-type current (An et al. 2000 ; Rosati et al. 2001 ; Kuo et al. 2001 ; Bähring et al. 2001 ; Guo et al. 2002a ; Patel et al. 2002 . KChIPs are calcium-binding proteins with four EF-hands that slow inactivation kinetics and accelerate recovery kinetics of Kv4 channels. (Patel )
Kcnip2 (also known as KCHIP2; MGC17241; DKFZp566L1246) encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belongs to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified from this gene.
Kcnip2 : Kv channel-interacting protein 2
NS5806 modulated K(V)4 channel gating depending on the presence of KChIP2, suggesting that NS5806 can potentially be used to address the molecular composition as well as the physiological role of cardiac I(to). ( Lundby )
KChIP2 expression in the t-tubules and the nucleus of heart muscle cells (in human and canine left ventricle) (Deschenes )
The functional effects of all of the KChIP2 splice variants on hKv4.3 current decay expressed in mammalian cells diminish rather than enhance the mimicry of cardiac Ito current. Although mouse KChIP2 was shown to be necessary for expression of Ito in mouse heart (Kuo , other data cast doubt on the notion that KChIP2 alone is responsible for the density gradient and biophysical features of native human and canine cardiac Ito. (Deschênes )
The predominant effects of all 3 KChIP2 splice variants on hKv4.3-encoded current are to increase the density, slow the current decay in a Ca2+-dependent manner, and hasten recovery from inactivation in a splice variant–specific fashion. (Deschenes )