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Elucidating KChIP effects on Kv4.3 inactivation and recovery kinetics with a minimal KChIP2 isoform.
Patel SP
,
Campbell DL
,
Strauss HC
.
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Kv channel interacting proteins (KChIPs) are Ca(2+)-binding proteins with four EF-hands. KChIPs modulate Kv4 channel gating by slowing inactivation kinetics and accelerating recovery kinetics. Thus, KChIPs are believed to be important regulators of Kv4 channels underlying transient outward K(+) currents in many excitable cell types. We have cloned a structurally minimal KChIP2 isoform (KChIP2d) from ferret heart. KChIP2d corresponds to the final 70 C-terminal amino acids of other KChIPs and has only one EF-hand. We demonstrate that KChIP2d is a functional KChIP that both accelerates recovery and slows inactivation kinetics of Kv4.3, indicating that the minimal C-terminus can maintain KChIP regulatory properties. We utilize KChIP2d to further demonstrate that: (i) the EF-hand modulates effects on Kv4.3 inactivation but not recovery; (ii) Ca(2+)-dependent effects on Kv4.3 inactivation are mediated through a mechanism reflected in the slow time constant of inactivation; and (iii) a short stretch of amino acids exclusive of the EF-hand partially mediates Ca(2+)-independent effects on recovery. Our results demonstrate that distinct regions of a KChIP molecule are involved in modulating inactivation and recovery. The potential ability of KChIP EF-hands to sense intracellular Ca(2+) levels and transduce these changes to alterations in Kv4 channel inactivation kinetics may serve as a mechanism allowing intracellular Ca(2+) transients to modulate repolarization. KChIP2d is a valuable tool for elucidating structural domains of KChIPs involved in Kv4 channel regulation.
An,
Modulation of A-type potassium channels by a family of calcium sensors.
2000, Pubmed,
Xenbase
An,
Modulation of A-type potassium channels by a family of calcium sensors.
2000,
Pubmed
,
Xenbase
Bähring,
Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and gating.
2001,
Pubmed
Beck,
Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein.
2002,
Pubmed
,
Xenbase
Bourne,
Immunocytochemical localization and crystal structure of human frequenin (neuronal calcium sensor 1).
2001,
Pubmed
Brahmajothi,
Distinct transient outward potassium current (Ito) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes.
1999,
Pubmed
Comer,
Cloning and characterization of an Ito-like potassium channel from ferret ventricle.
1994,
Pubmed
,
Xenbase
Deschênes,
Regulation of Kv4.3 current by KChIP2 splice variants: a component of native cardiac I(to)?
2002,
Pubmed
Guo,
Role of heteromultimers in the generation of myocardial transient outward K+ currents.
2002,
Pubmed
Guo,
Modulation of Kv4-encoded K(+) currents in the mammalian myocardium by neuronal calcium sensor-1.
2002,
Pubmed
Ikura,
Calcium binding and conformational response in EF-hand proteins.
1996,
Pubmed
Jerng,
K+ channel inactivation mediated by the concerted action of the cytoplasmic N- and C-terminal domains.
1997,
Pubmed
,
Xenbase
Jerng,
Inactivation gating of Kv4 potassium channels: molecular interactions involving the inner vestibule of the pore.
1999,
Pubmed
,
Xenbase
Kuo,
A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia.
2001,
Pubmed
Lewit-Bentley,
EF-hand calcium-binding proteins.
2000,
Pubmed
Linse,
Determinants that govern high-affinity calcium binding.
1995,
Pubmed
Näbauer,
Regional differences in current density and rate-dependent properties of the transient outward current in subepicardial and subendocardial myocytes of human left ventricle.
1996,
Pubmed
Nakamura,
A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4 K+-currents.
2001,
Pubmed
,
Xenbase
Patel,
Heterogeneous expression of KChIP2 isoforms in the ferret heart.
2002,
Pubmed
,
Xenbase
Peterson,
Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels.
1999,
Pubmed
Pitt,
Molecular basis of calmodulin tethering and Ca2+-dependent inactivation of L-type Ca2+ channels.
2001,
Pubmed
,
Xenbase
Rosati,
Regulation of KChIP2 potassium channel beta subunit gene expression underlies the gradient of transient outward current in canine and human ventricle.
2001,
Pubmed
,
Xenbase
Takimoto,
KChIPs (Kv channel-interacting proteins)--a few surprises and another.
2002,
Pubmed
Wang,
Kinetic properties of Kv4.3 and their modulation by KChIP2b.
2002,
Pubmed
,
Xenbase
Xu,
Four kinetically distinct depolarization-activated K+ currents in adult mouse ventricular myocytes.
1999,
Pubmed
