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

Abstract

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