Down-regulation of the large-conductance Ca(2+)-activated K+ channel, K(Ca)1.1 in the prostatic stromal cells of benign prostate hyperplasia.
Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel encoded by K(Ca)1.1 plays an important role in the control of smooth muscle tone by modulating membrane potential and intracellular Ca(2+) mobilization. BK(Ca) channel is functionally expressed in prostatic smooth muscle cells, and is activated by α(1)-adrenoceptor agonists. The main objective of this study was to elucidate the pathophysiological significance of changes in prostatic K(Ca)1.1 expressions in benign prostatic hyperplasia (BPH). Our previous study has shown that K(Ca)3.1 encoding intermediate-conductance K(Ca) (IK(Ca)) channel is up-regulated in stromal cells of implanted urogenital sinuses (UGSs) of stromal hyperplasia BPH model rats and in those of prostatic tissues from BPH patients. In the present study, the results from real-time polymerase chain reaction (PCR), Western blot, and immunohistochemical analyses showed significant down-regulation of K(Ca)1.1 transcripts and proteins and negative correlation between K(Ca)1.1 and K(Ca)3.1 transcript expressions in prostatic stromal cells of both BPH model rats and BPH patients. Corresponding to down-regulation of K(Ca)1.1 expression in stromal cells of implanted UGSs, membrane depolarization by application of the BK(Ca) channel blocker was disappeared. Down-regulation of K(Ca)1.1 may be involved in the phenotype switch from contractile profile to proliferative one in prostatic stromal cells of BPH patients.
Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan.
Satomi
S
Niwa
Susumu
S
Ohya
Yoshiyuki
Y
Kojima
Shoichi
S
Sasaki
Hisao
H
Yamamura
Motomu
M
Sakuragi
Kenjiro
K
Kohri
Yuji
Y
Imaizumi
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011467:Prostate / Q000166:cytology* / Q000187:drug effects / Q000503:physiopathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers