Erschienen in:
01.03.2015 | Original Contribution
Interaction of DPP10a with Kv4.3 channel complex results in a sustained current component of human transient outward current I
to
verfasst von:
K. Turnow, K. Metzner, D. Cotella, M. J. Morales, M. Schaefer, T. Christ, U. Ravens, E. Wettwer, S. Kämmerer
Erschienen in:
Basic Research in Cardiology
|
Ausgabe 2/2015
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Abstract
The sustained component of the K+ outward current in human atrial myocytes is believed to be due to the slowly inactivating ultra-rapid potassium current I
Kur and not to the fast inactivating transient outward current I
to. Here we provide evidence for contribution of I
to to this late current due to the effects of dipeptidyl peptidase-like protein (DPP) 10 (DPP10a) interacting with Kv4.3 channels. We studied the late current component of I
to in human atrial myocytes and CHO cells co-expressing Kv4.3 or Kv4.3/KChIP2 (control) and DPP proteins using voltage-clamp technique and a pharmacological approach. A voltage dependent and slowly inactivating late current (43 % of peak amplitude) could be observed in atrial myocytes. We found a similar current in CHO cells expressing Kv4.3/KChIP2 + DPP10a, but not in cells co-expressing Kv4.3 + DPP or Kv4.3/KChIP2 + DPP6-S. Assuming that DPP10a influences atrial I
to, we detected DPP10 expression of three alternatively spliced mRNAs, DPP10 protein and colocalization of Kv4.3 and DPP10 proteins in human atrial myocytes. DPP10a did not affect properties of expressed Kv1.5 excluding a contribution to the sustained I
Kur in atrial cells. To test for the contribution of Kv4-based I
to on sustained K+ outward currents in human atrial myocytes, we used 4-AP to block I
Kur, in combination with Heteropoda toxin 2 to block Kv4 channels. We could clearly separate an I
to fraction of about 19 % contributing to the late current in atrial myocytes. Thus, the interaction of DPP10a, expressed in human atrium, with Kv4.3 channels generates a sustained current component of I
to, which may affect late repolarization phase of atrial action potentials.