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Expression and function of the small-conductance Ca

International urology and nephrology (2017-04-19)
Ning Li, Honglin Ding, Xiaoning He, Zizheng Li, Yili Liu
RÉSUMÉ

Overactive bladder (OAB), usually accompanied by partial bladder outlet obstruction (PBOO), is associated with detrusor overactivity (DO) which is related to the increased urinary bladder smooth muscle (UBSM) cells excitability. Small-conductance Ca Cystometry indicated that DO was achieved 2 weeks after PBOO in female guinea pigs. Using this animal model, we conducted single-cell quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and patch-clamp electrophysiology. The single-cell qRT-PCR experiments indicated the reduced SK channel mRNA expression in PBOO UBSM cells. Patch-clamp studies revealed that NS309 had a diminished effect on resting membrane potential hyperpolarization via the activation of SK channels in PBOO UBSM cells. Moreover, attenuated whole-cell SK channel currents were demonstrated in PBOO UBSM cells. The attenuated expression and function of SK channels, which results in the increased UBSM cells excitability and contributes to DO, was discovered in PBOO UBSM cells, suggesting that SK channels might be potential therapeutic targets for the control of OAB.

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NS309, ≥98% (HPLC), solid