Modulation of human Kv1.5 channel kinetics by N-cadherin.
Kv1.5 is expressed in multiple tissues including heart, brain, macrophages, as well as vascular, airway, and intestinal smooth muscle cells. Kv1.5 currents contribute to cardiac repolarization. In cardiac myocytes Kv1.5 colocalizes with N-cadherin. As Kv1.5 expression increases following establishment of cell-cell contacts and N-cadherin influences the activity of other ion channels, we explored whether N-cadherin participates in the regulation of Kv1.5 activity. To this end, we expressed Kv1.5 in Xenopus oocytes with or without additional expression of N-cadherin. Coexpression of N-cadherin was followed by a approximately 2- to 3-fold increase of Kv1.5 induced current. The effect of N-cadherin was not paralleled by significant alterations of Kv1.5 channel abundance within the oocyte cell membrane but resulted primarily from accelerated recovery from inactivation. In conclusion, N-cadherin modifies Kv1.5 channel activity and is thus a novel candidate signaling molecule participating in the regulation of a variety of functions including cardiac action potential and vascular tone.
Koutsouki
Evgenia
E
Department of Physiology, University of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
Lam
Rebecca S
RS
Seebohm
Guiscard
G
Ureche
Oana N
ON
Ureche
Liviu
L
Baltaev
Ravshan
R
Lang
Florian
F
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D051666:Kv1.5 Potassium Channel / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D009865:Oocytes / Q000502:physiology*; D014982:Xenopus laevis
D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel