Activation of the Ca2+-Activated K+ Channel via Protein Kinase A-Dependent Phosphorylation in Human Prostatic Smooth Muscle Cells

Background: We investigated the functional importance of the Ca²⁺-activated K⁺ channel (K_Ca-channel) of human prostatic smooth muscle cells in cyclic adenosine 3', 5'-monophosphate (cAMP)-induced relaxation, to clarify signal transduction pathways and intracellular mechanisms of relaxation in prostatic smooth muscle.
Methods: Using the patch-clamp technique, we characterized the K_Ca-channel of cultured human prostatic smooth muscle cells. We also investigated the effects on the K_Ca-channels of forskolin, an activator of adenylate cyclase, amrinone, a phosphodiesterase inhibitor, and protein kinase A (A-kinase)-dependent phosphorylation.
Results: Single-channel current recordings from cultured human prostatic smooth muscle cells revealed the presence of K_Ca-channels (conductance 296.7±5.67 pS, n = 7). In cell-attached patch configurations, the K_Ca-channel was activated by forskolin (1CH mol/L) and amrinone (10⁻⁴ mol/L). In inside-out patch configurations, it was activated by catalytic subunits of A-kinase (10 U/mL).
Conclusions: We conclude that the K_Ca-channel of human prostatic smooth muscle cells is regulated by intracellular cAMP levels and that A-kinase mediates the cAMP-induced activation of the K_Ca-channel. This regulation of the K_Ca-channel by cAMP may at least partially explain cAMP-induced prostatic smooth muscle relaxation and the effectiveness of certain drugs for treatment of obstruction in benign prostatic hyperplasia.