TITLE:
Expression of Large Conductance, Voltage- and Ca2+-Activated K+ (BK) Channels in Human Urinary Bladder: Alteration of Subunit Expression Profile in Association with Bladder Outlet Obstruction
AUTHORS:
Hidenori Zakoji, Hideki Kobayashi, Mitsuharu Yoshiyama, Masayuki Takeda, Isao Araki
KEYWORDS:
BK Channel; Overactive Bladder; Bladder Outlet Obstruction
JOURNAL NAME:
Open Journal of Urology,
Vol.3 No.2,
May
15,
2013
ABSTRACT:
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.