K ATP channels mediate the β 2-adrenoceptor agonist-induced relaxation of rat detrusor muscle

Abstract

We propose that ATP-sensitive K + (K ATP) channels are normally inactive but involved in β 2-adrenoceptor stimulated relaxation of the rat bladder. Spontaneous detrusor muscle contractions were unaffected by glibenclamide (K ATP channel blocker) but were reduced when pinacidil (K ATP channel opener) concentrations exceeded 10 −5 M. Inhibition by β 2-adrenoceptor agonist clenbuterol (10 −6 M) of 1 Hz electrical field stimulated contractions was abolished by glibenclamide (10 −6 M). Glibenclamide (10 −6 M) decreased forskolin-induced relaxation (10 −9–10 −4 M) in bladder muscle stimulated with 1 Hz electrical field. In the presence glibenclamide (10 −6 M) or myristoylated protein kinase A inhibitor (2×10 −6 M), clenbuterol (10 −9–10 −5 M) failed to inhibit bladder contraction in response to 1 Hz electrical field stimulation. Therefore, K ATP channel opening and the subsequent hyperpolarization of cell membranes in response to β 2-adrenoceptor activation is mediated by raised cyclic-AMP levels and activation of protein kinase A. This counteracts ATP-stimulated depolarization in bladder muscle, thereby reducing cell contraction.