Attenuated regulatory function of the small-conductance Ca2+-activated K+ channel in detrusor smooth muscle cells excitability in an obese rat model.

PURPOSE: Overactive bladder (OAB) is related to detrusor overactivity (DO), which is caused by the increased detrusor smooth muscle (DSM) cells excitability. Small-conductance Ca2+-activated K+ (SK) channels is a fundamental regulator of excitability and contractility in DSM cells. Obesity-related OAB is associated with the decreased expression and regulatory function of SK channels in DSM layer. However, the regulation role of SK channels in obesity-related OAB DSM cell excitability is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM cells.

METHODS: Female Sprague-Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. We performed urodynamic study, single-cell quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and patch-clamp electrophysiology.

RESULTS: Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. Single-cell qRT-PCR experiments discovered the decreased mRNA expression level of SK channel in DSM cell from HFD rats. Patch-clamp studies revealed that NS309, a SK channel activator, had an attenuated effect on membrane potential hyperpolarization in HFD DSM cells. In addition, the reduced whole cell SK channel currents were recorded in HFD DSM cells.

CONCLUSIONS: Attenuated SK channels expression and function, which results in the increased DSM cells excitability and contributes to DO, is discovered in obesity-related OAB DSM cells, suggesting that SK channels might be potential therapeutic targets to control OAB.