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  • Review Article
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Role of potassium ion channels in detrusor smooth muscle function and dysfunction

Nature Reviews Urology volume 9, pages 30–40 (2012)Cite this article

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Abstract

Contraction and relaxation of the detrusor smooth muscle (DSM), which makes up the wall of the urinary bladder, facilitates the storage and voiding of urine. Several families of K+ channels, including voltage-gated K+ (KV) channels, Ca2+-activated K+ (KCa) channels, inward-rectifying ATP-sensitive K+ (Kir, KATP) channels, and two-pore-domain K+ (K2P) channels, are expressed and functional in DSM. They control DSM excitability and contractility by maintaining the resting membrane potential and shaping the action potentials that determine the phasic nature of contractility in this tissue. Defects in DSM K+ channel proteins or in the molecules involved in their regulatory pathways may underlie certain forms of bladder dysfunction, such as overactive bladder. K+ channels represent an opportunity for novel pharmacological manipulation and therapeutic intervention in human DSM. Modulation of DSM K+ channels directly or indirectly by targeting their regulatory mechanisms has the potential to control urinary bladder function. This Review summarizes our current state of knowledge of the functional role of K+ channels in DSM in health and disease, with special emphasis on current advancements in the field.

Key Points

  • K+ channels control the excitability and contractility of detrusor smooth muscle (DSM)

  • Large-conductance voltage-activated and Ca2+-activated (BK) channels, small-conductance Ca2+-activated K+ (SK) channels, two-pore-domain K+ (K2P) channels and voltage-gated K+ (KV) channels are important regulators of DSM function

  • BK channelopathy is implicated in some forms of detrusor overactivity and related overactive bladder

  • BK, SK, K2P and KV channels represent novel targets for pharmacological or gene-therapy-mediated control of DSM function

  • The KV channel family is the most diverse; therefore, it is likely that many new DSM KV channels, some of them bladder-specific, are yet to be discovered

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Figure 1: Illustration of the transmembrane architecture and subunit stoichiometry of the K+ channel types expressed in detrusor smooth muscle cells.
Figure 2: Schematic illustration of the detrusor smooth muscle action potential and the roles of various K+ channels in determining resting membrane potential and action potential.
Figure 3: Hypothetical pharmacological dissection of KCa and KV currents in detrusor smooth muscle cells using various K+ channel-selective inhibitors.
Figure 4: Schematic illustration of the functional coupling between the β3-AR and the BK channel in a detrusor smooth muscle cell.

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Acknowledgements

The author thanks the members of his research group (Drs J. Malysz, K. Hristov, S. Parajuli, W. Xin, Ms A. Smith, Ms R. Soder, Mr S. Afeli and Mr Q. Cheng), as well as Dr J. Schnellmann for the critical evaluation of the manuscript. This work was supported by grants from the NIH (DK084284 and DK083687).

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  1. Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Coker Life Sciences Building, Room 609D, 715 Sumter Street, Columbia, 29208, SC, USA

    Georgi V. Petkov

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Petkov, G. Role of potassium ion channels in detrusor smooth muscle function and dysfunction. Nat Rev Urol 9, 30–40 (2012). https://doi.org/10.1038/nrurol.2011.194

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