Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel

Andrea L Meredith1, Kevin S Thorneloe, Matthias E Werner

  • 1Department of Molecular and Cellular Physiology and the Howard Hughes Medical Institute, 279 Campus Drive, Stanford University, Stanford, CA 94305, USA.

Insights

Large conductance voltage- and calcium-activated potassium (BK) channels are crucial for urinary bladder function. Their absence in mice led to enhanced bladder contractions and overactive bladder symptoms, indicating their therapeutic potential.

Area of Science:

  • Physiology
  • Pharmacology
  • Urology

Background:

  • Large conductance voltage- and calcium-activated potassium (BK) channels regulate smooth muscle excitability.
  • BK channels are implicated in urinary bladder function and are potential therapeutic targets for overactive bladder.
  • The specific role of BK channels in bladder smooth muscle requires further elucidation.

Purpose of the Study:

  • To investigate the role of the BK channel in urinary bladder function.
  • To determine the effects of BK channel deletion on bladder smooth muscle activity and voiding behavior.

Main Methods:

  • Generation of mSlo1 gene-deleted (Slo(-/-)) mice lacking the pore-forming subunit of BK channels.
  • Electrophysiological recordings to assess BK currents in urinary bladder smooth muscle cells.
  • Measurement of spontaneous and nerve-evoked bladder contractions.
  • Observation of urination frequency in wild-type and Slo(-/-) mice.

Main Results:

  • Slo(-/-) mice exhibited normal viability but moderate ataxia.
  • Urinary bladder smooth muscle cells from Slo(-/-) mice lacked BK currents, while other potassium currents and calcium transients remained unaffected.
  • Absence of BK channels resulted in significantly enhanced spontaneous and nerve-evoked bladder contractions.
  • Slo(-/-) mice displayed a marked increase in urination frequency, indicative of overactive bladder.

Conclusions:

  • BK channels play a critical role in regulating urinary bladder smooth muscle function.
  • Dysfunction or absence of BK channels leads to enhanced bladder contractility and overactive bladder symptoms, including urinary incontinence.
  • Targeting BK channels represents a promising therapeutic strategy for treating overactive bladder.

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