Down-Regulation of the Large-Conductance Ca²⁺-Activated K⁺ Channel, K_Ca1.1 in the Prostatic Stromal Cells of Benign Prostate Hyperplasia

Abstract

Large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel encoded by K_Ca1.1 plays an important role in the control of smooth muscle tone by modulating membrane potential and intracellular Ca²⁺ mobilization. BK_Ca channel is functionally expressed in prostatic smooth muscle cells, and is activated by α₁-adrenoceptor agonists. The main objective of this study was to elucidate the pathophysiological significance of changes in prostatic K_Ca1.1 expressions in benign prostatic hyperplasia (BPH). Our previous study has shown that K_Ca3.1 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_Ca1.1 transcripts and proteins and negative correlation between K_Ca1.1 and K_Ca3.1 transcript expressions in prostatic stromal cells of both BPH model rats and BPH patients. Corresponding to down-regulation of K_Ca1.1 expression in stromal cells of implanted UGSs, membrane depolarization by application of the BK_Ca channel blocker was disappeared. Down-regulation of K_Ca1.1 may be involved in the phenotype switch from contractile profile to proliferative one in prostatic stromal cells of BPH patients.