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 (10(-4) 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.
Department of Urology, Tokushima University School of Medicine, Japan.
Y
Y
Kurokawa
K
K
Kojima
H
H
Kanayama
S
S
Kagawa
K
K
Minami
Y
Y
Nakaya
D000262:Adenylyl Cyclases / Q000378:metabolism; D000676:Amrinone / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000601:surgery; D015398:Signal Transduction / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D005576:Colforsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D000676:Amrinone; D002118:Calcium