Acta Pharmacologica Sinica 2008 June; 29 (6): 653-660; doi: 10.1111/j.1745-7254.2008.00804.x

Aim: Several β-subunits have been suggested to modulate the electrophysiological properties of the transient outward current (I_to) 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 I_to. The present study is to investigate how I_to 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 I_to. 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 I_to. Both KChIP2c and KCNE2 simultaneously participate in recapitulation of the electrophysiological properties of I_to in cardiac myocytes.

Keywords: transient outward current; Kv4.2; K⁺-channel interacting protein; KCNE2; electrophysiology