Neuropharmacology

Co-expression of KCNE2 and KChIP2c modulates the electrophysiological properties of Kv4.2 current in COS-7 cells

Abstract

Aim:

Several β-subunits have been suggested to modulate the electrophysiological properties of the transient outward current (Ito) in cardiac myocytes, including the obligatory β-subunit K+-channel interacting protein (KChIP2) and KCNE2. However, neither KChIP2 nor KCNE2 modulation of Kv4.x (x=2 and/or 3) can fully recapitulate the electrophysiological properties of native Ito. The present study is to investigate how Ito current is modulated when both KChIP2 and KCNE2 are co-expressed.

Methods:

Kv4.2, KChIP2c, and KCNE2 cDNA were simultaneously transfected into COS-7 cells at a molar ratio of 3:1:1. Whole-cell currents were recorded by the patch-clamp method.

Results:

In comparison with the current regulated by KChIP2c alone, the co-expression of KCNE2 further slowed Kv4.2 current inactivation kinetics, but diminished KChIP2c-induced positive shift of the voltage-dependent activation of Kv4.2 current. Importantly, co-expression of KCNE2 accelerated the current recovery from inactivation, and caused an “overshoot” of peak current amplitude during Kv4.2 current recovery, a phenomenon which has been uniquely described for human Ito. However, co-expression of KCNE2 exerted no further effect on Kv4.2 current amplitude, the rate of Kv4.2 current activation and voltage-dependent inactivation.

Conclusion:

Co-expression of Kv4.2 with KChIP2c and KCNE2, but not with KChIP2c or KCNE2 alone, yields a current profile similar to native Ito. Both KChIP2c and KCNE2 simultaneously participate in recapitulation of the electrophysiological properties of Ito in cardiac myocytes.

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Correspondence to Jie Liu.

Additional information

Project supported by the National Natural Science Foundation of China (No 30570418 and 30570940).

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Liu, Wj., Wang, Ht., Chen, Ww. et al. Co-expression of KCNE2 and KChIP2c modulates the electrophysiological properties of Kv4.2 current in COS-7 cells. Acta Pharmacol Sin 29, 653–660 (2008). https://doi.org/10.1111/j.1745-7254.2008.00804.x

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Keywords

  • transient outward current
  • Kv4.2
  • K+-channel interacting protein
  • KCNE2
  • electrophysiology

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