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Modulation of human Kv1.5 channel kinetics by N-cadherin.

Evgenia Koutsouki, Rebecca S Lam, Guiscard Seebohm, Oana N Ureche, Liviu Ureche, Ravshan Baltaev, Florian Lang

Biochem. Biophys. Res. Commun., 2007 Nov 9 , 363, 18-23

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.