Endothelial K + channel lacks the Ca 2+ sensitivity‐regulating β subunit

Abstract

Hyperpolarizing large‐conductance, Ca 2+ ‐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 α subunits and modulatory β 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 endothe‐lium of porcine aortic tissue slices. The BK opener DHS‐I (0.05–0.3 μmol/l). stimulating BK activity only in the presence of β subunits. had no effect on BK in endothelium whereas the α subunit selective BK opener NS1619 (20 μmol/l) markedly increased channel activity. Correspondingly. mRNA expression of the β subunit was undetectable in endothelium. whereas α subunit expression was demonstrated. To investigate the functional role of β subunits. we transfected the β subunit into a human endothelial cell line (EA.hy 926). β subunit expression resulted in an increased Ca 2+ sensitivity of BK activity: the potential of half‐maximal activation (Vw 2 ) shifted from 73.4 mV to 49.6 mV at 1 μmol/l [Ca 2+ ] i and an decrease of the EC 50 value for [Ca 2+ ] i by 1 μMat + 60 mV was observed. This study demonstrates that BK channels in endothelium are composed of α subunits without association to β subunits. The lack of the β subunit indicates a substantially different channel regulation in endothelial cells compared to vascular smooth muscle cells.—Papassotiriou. J.. Kohler. R.. Prenen. J.. Krause. H.. Akbar. M.. Egger‐mont. J.. Paul. M.. Distler. A.. Nilius. B.. Hoyer. J. Endothelial K+ channel lacks the Ca 2 + sensitivity‐regulating β subunit. FASEBJ. 14. 885–894 (2000)