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Endothelial K⁺ channel lacks the Ca²⁺ sensitivity-regulating ß subunit

J. PAPASSOTIRIOU^*, R. KÖHLER^*, J. PRENEN, H. KRAUSE, M. AKBAR^*, J. EGGERMONT, M. PAUL^§, A. DISTLER^*, B. NILIUS and J. HOYER^*1

^* Abteilung für Nephrologie,
Abteilung für Urologie,
^§ Institut für Klinische Pharmakologie, UKBF, Freie Universität Berlin, 12200 Berlin, Germany; and
Laboratorium voor Fysiologie, Campus Gasthuisberg, KU Leuven, 3000 Leuven, Belgium

¹Correspondence: Abt. für Allg. Innere Medizin und Nephrologie, Med. Klinik und Poliklinik, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: hoy{at}zedat.fu-berlin.de

Hyperpolarizing large-conductance, Ca²⁺-activated K⁺ channels (BK) are important modulators of vascular smooth muscle and endothelial cell function. In vascular smooth muscle cells, BK are composed of pore-forming subunits and modulatory ß subunits. However, expression, composition, and function of BK subunits in endothelium have not been studied so far. In patch-clamp experiments we identified BK (283 pS) in intact endothelium of porcine aortic tissue slices. The BK opener DHS-I (0.05–0.3 µmol/l), stimulating BK activity only in the presence of ß subunits, had no effect on BK in endothelium whereas the subunit selective BK opener NS1619 (20 µmol/l) markedly increased channel activity. Correspondingly, mRNA expression of the ß subunit was undetectable in endothelium, whereas subunit expression was demonstrated. To investigate the functional role of ß subunits, we transfected the ß subunit into a human endothelial cell line (EA.hy 926). ß subunit expression resulted in an increased Ca²⁺ sensitivity of BK activity: the potential of half-maximal activation (V_1/2) shifted from 73.4 mV to 49.6 mV at 1 µmol/l [Ca²⁺]_i and an decrease of the EC₅₀ value for [Ca²⁺]_i by 1 µM at +60 mV was observed. This study demonstrates that BK channels in endothelium are composed of subunits without association to ß subunits. The lack of the ß subunit indicates a substantially different channel regulation in endothelial cells compared to vascular smooth muscle cells.—Papassotiriou, J., Köhler, R., Prenen, J., Krause, H., Akbar, M., Eggermont, J., Paul, M., Distler, A., Nilius, B., Hoyer, J. Endothelial K⁺ channel lacks the Ca²⁺ sensitivity-regulating ß subunit.

Key Words: endothelium • Slo • maxi K • channel subunit • patch-clamp • beta subunit expression

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