Background/Aim: 

The time course of outward currents in human atrial cardiomyocytes consists of several components suggesting that multiple channels contribute. The late component of outward current is thought to be due to the more slowly inactivating ultra rapid potassium current I_Kur and not to the fast inactivating I_to. However, recent studies of DPPs acting as accessory b-subunits of Kv4-encoded K⁺ channels provide evidence that I_to might also contribute to late current. Jerng et al. 2009 showed that a conserved intracellular N-terminal motif of DPPs is functional for the hastening of inactivation in Kv4.2 channels by a pore-blocking mechanism. This delays inactivation of Kv4 channels producing a late current component. Here we have investigated whether DPPs are partly responsible for the late current in atrial I_to as well as putative interdependence of the rapid early and the slow late current components.

Methods: 

Late component of I_to was studied in heterologous expression systems (CHO-cells) using standard voltage clamp techniques. CHO cells were stably transfected with I_to channel complex Kv4.3/KChIP2 and transiently co-expressed with isoforms of either DPP6 and DPP10 or domain truncations of DPP10.

Results: 

In CHO cells expressing Kv4.3/KChIP2 plus DPP10, we identified a late slowly inactivating component ("I_to-late") four fold larger than in control cells without DPP10 expression. Cells co-expressing DPP6, however, did not show a significant I_to-late component. Comparing the influence of different domains of DPP10 on I_to-late, only the intracellular plus the transmembrane sequence resulted in a significant higher late component and fastened inactivation whereas the extracellular plus the transmembrane domain did not produce these effects.

Conclusion: 

We provide evidence that the late current component in I_to is specifically induced by the intracellular domain of DPP10 assumed to be also responsible for fast phase inactivation provoked by the N-terminus. As DPP6 also leads to an acceleration of the early phase of rapid inactivation but not to a late sustained current component we suggest that either the hastening effect of DPP6 on I_to is not strong enough or that both effects, fast inactivation and the appearance of a late component are independent phenomena.