Altered expression of calcium‐activated K and Cl channels in detrusor overactivity of rats with partial bladder outlet obstruction

Abstract

OBJECTIVE To evaluate the activity of large‐ and small‐conductance calcium‐activated potassium channels (BKCa, SKCa) and calcium‐activated chloride channels (ClCa) in detrusor overactivity (DO) cells after partial bladder outlet obstruction (PBOO) in rats. MATERIALS AND METHODS Thirteen female Wistar rats with DO caused by PBOO were studied simultaneously with eight sham‐operated rats. The expression of KCa and ClCa channels was assessed by reverse transcription‐polymerase chain reaction, and the function of the two groups compared. RESULTS In the DO cells the expression of BKCa, SKCa2 and SKCa3 was lower, and that of ClCa channels higher, than in the control group cells. Using confocal laser scanning microscopic analysis, the function of BKCa and SKCa channels was suppressed, and that of ClCa channels was enhanced in DO group cells. KCa and ClCa effectors altered the cell membrane potentials more significantly in the DO cells than in the control cells, indicating a decrease in KCa and an increase in ClCa in DO group in either iso‐ or hypo‐osmolar medium. Moreover, the change in BKCa, SKCa and ClCa channel activators in DO cells showed a more excitable state in hypo‐osmolar medium than in iso‐osmolar medium. CONCLUSION In DO myocytes after PBOO, the expression and function of KCa channels were decreased, and those of ClCa channels increased. These changes all provoke greater cell excitability, and could partly account for the DO.

Spontaneous and evoked contractions are regulated by PKC-mediated signaling in detrusor smooth muscle: involvement of BK channels

“…Detrusor smooth muscle (DSM) strips from PBOO bladders show smooth muscle hypertrophy and remodeling with alteration in the signal transduction pathways that regulate force generation by DSM (5,17). More recent studies have shown that, along with an increase in mass, changes in regulatory proteins such as protein kinase C (PKC) and large conductance Ca 2ϩ -activated potassium channels (BK) are increasingly being linked to this PBOO-associated altered phenotype.…”

“…More recent studies have shown that, along with an increase in mass, changes in regulatory proteins such as protein kinase C (PKC) and large conductance Ca 2ϩ -activated potassium channels (BK) are increasingly being linked to this PBOO-associated altered phenotype. Both PKC and BK channels are downregulated in PBOO in rabbits, rats, and patients with BPH (5,6,17). The downregulation of BK channels has been linked to higher levels of myosin light chain phosphorylation, which is believed to play a role in detrusor overactivity (DO), and NVC associated with PBOO (5).…”

Role of ion channels in bladder function and voiding disorders

“…Conversely, bladder injection of the hSlo/pc DNA3 gene for the BK pore in rats reduced detrusor overactivity after partial bladder outlet obstruction [14]. Consistent with these observations, obstructed rats demonstrate reduced expression of BK and SK channels [15]. Another clinically relevant observation is that irritation of the bladder with a weak acid activates BK channels, possibly to counteract overactivity [16].…”

Is benign prostatic obstruction surgery indicated for improving overactive bladder symptoms in men with lower urinary tract symptoms?

“…Furthermore, the downregulation of the b-subunit was associated with an abnormal increase of myosin light chain phosphorylation. In another study in rats, Li et al [25] have shown that bladder outlet obstruction led to a lower expression of large and small-conductance calcium-activated potassium channels in the detrusor muscle compared with controls. They were also able to demonstrate that calcium-activated chloride channels activity was increased compared with controls leading to greater excitability of the cells and being potentially responsible for detrusor contractions.…”