BIPHASIC ACTION OF PHENYLEPHRINE ON THE CA2-ACTIVATED K+ CHANNEL OF HUMAN PROSTATIC SMOOTH-MUSCLE CELLS()

The elevation of cytosolic Ca2+ ([Ca2+](i)) is known to regulate smoot h muscle contractility, A physiological concentration of phenylephrine induced the elevation in [Ca2+](i) of human prostatic smooth muscle c ells; however, contraction of prostatic tissues in vitro needs a highe r concentration of phenylephrine than the physiological level. To inve stigate this discrepancy, we investigated the functional importance of the Ca2+-activated K+ channel (K-Ca channel) of human prostatic smoot h muscle cells in phenylephrine-induced contraction. Using the patch-c lamp technique, the K-Ca channel of human prostatic smooth muscle cell s was activated by phenylephrine at a physiological concentration (10( -7)-10(-5) M) but was inhibited at a higher concentration (10(-4)-10(- 3) M). Phenylephrine (10(-3) M) also inhibited the K-Ca channel which was activated by 10 mu M A23187, a calcium ionophore, Similar inhibiti on was obtained with 1 mu M phorbol 12-myristate 13-acetate, an activa tor of protein kinase C (C-kinase). Both inhibitions were reversed by subsequent application of 1 nM staurosporine, a protein kinase inhibit or, These results suggested that C-kinase mediated the phenylephrine-i nduced inhibition of the K-Ca channel. In this study, a physiological concentration of phenylephrine induced activation of the K-Ca channel of human prostatic smooth muscle cells, which brought about membrane h yperpolarization and relaxation of human prostatic smooth muscle cells . The regulation of the K-Ca channel by phenylephrine may explain the need of a high concentration of phenylephrine for the contraction of p rostatic tissue.