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.
Highlights
Overactive bladder (OAB) is a common pathologic condition resulting from a neurogenic or non-neurogenic etiology that can be related to outflow obstruction and/or aging, but most cases are idiopathic [1]
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)
Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis revealed the presence of α, β1, and β4-subunit genes of BK channel in the mucosal layer, αand β1-subunit in the muscle layer
Summary
Overactive bladder (OAB) is a common pathologic condition resulting from a neurogenic or non-neurogenic etiology that can be related to outflow obstruction and/or aging, but most cases are idiopathic [1]. To elucidate the mechanism of OAB is required, and there is a clinical need for an effective drug to treat OAB. The ion channels such as calcium channels and potassium channels, play important roles in determining the functional properties and are obvious targets for treatment of overactive bladder [4]. Potassium channels play an important role for the membrane potential, and opening of the potassium channel leads to hyperpolarization of the membrane of smooth muscle cells [5]. It reduces the opening probability of ion channels which are OJU
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