Expression of Large Conductance, Voltage- and Casup2+/sup-Activated Ksup+/sup(BK) Channels in Human Urinary Bladder: Alteration of Subunit Expression Profile in Association with Bladder Outlet Obstruction

摘要

Purpose: Large conductance, voltage- and Ca2+-activated K+ (BK) channel is thought to have a central role to regulate urinary bladder smooth muscle functions, and its dysfunction may lead to increase of urination frequency and overactive bladder. The present study aims to investigate the expression pattern of BK channel subunits in the human urinary bladder, and how it changes in association with bladder outlet obstruction (BOO). Materials and Methods: Human bladders were obtained from 7 controls without prostatic enlargement and lower urinary tract symptoms and 4 BPH patients with clinically diagnosed overactive bladder who were verified by the International Prostate Symptom Score (IPSS) and prostate volume. The expression and location of BK channel protein complex was examined using immunohistochemistry with affinity-purified anti-BKα antibodies. A real-time RT-PCR was used to quantify the expression of each BK channel subunit (α and β1 - 4) gene in the mucosal and muscle layers of human urinary bladder. Results: Immunohistochemical staining for BK-α protein complex was localized in the muscle and submucosal regions of urinary bladder. RT-PCR analysis revealed the presence of α-, β1-, and β4-subunit genes of BK channel in the mucosal layer, α- and β1-subunit in the muscle layer. The expressions of α- and β1-subunit genes in the muscle (α: p = 0.0003, β1: p = 0.0003) and mucosal (α: p = 0.03, β1: p = 0.02) layers significantly decreased in BOO bladders compared with controls. The expression levels of α- and β1-subunit in mucosal layer were statistically correlated with storage score of IPSS (α;r = 0.84, p = 0.002, β1;r = 0.84, p = 0.002), and so were in muscle layer (α;r = 0.934, p 0.0001, β1;r = 0.917, p = 0.00018). Conclusions: BK channels, which are mainly composed of α- and β1-subunits, are expressed in both the mucosal and muscle layers of human urinary bladder. Decreased expression of BK channel in BOO might be implicated in the mechanisms underlying the development of overactive bladder.