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Calcium signalling in Cajal-like interstitial cells of the lower urinary tract

Nature Reviews Urology volume 11, pages 555–564 (2014)Cite this article

Subjects

Key Points

  • Interstitial cell of Cajal-like cells (ICC-LC) are found throughout the lower urinary tract (LUT), where they form a functional syncytium with nerves, smooth muscle cells and recently identified PDGFRα+ cells

  • ICC-LC are believed to function as electrical pacemakers in the urethra and prostate, and in the bladder they might act as intermediary cells to transduce nerve signals to smooth muscle cells

  • The generation of intracellular Ca2+ transients originating from the release of Ca2+ from the endoplasmic reticulum (ER) seems to be fundamental to the physiological functions of ICC-LC

  • Ca2+ release from the ER involves the activation of receptors sensitive to inositol 1,4,5-triphosphate and ryanodine. Propagation of this Ca2+ signal is subsequently supported by Ca2+ influx and mitochondrial Ca2+ handling of cytosolic Ca2+ levels

  • Several translational studies have revealed that ICC-LC might serve as valuable targets for LUT dysfunctions including overactive bladder and benign prostatic hyperplasia

  • The modulation of muscle excitability in the LUT depends on Ca2+ signalling originating in ICC-LC. Further examination of these events provides an approach to evaluate therapeutic agents on LUT function

Abstract

Interstitial cells of Cajal (ICC) serve several critical physiological roles in visceral smooth muscle organs, including acting as electrical pacemakers to modulate phasic contractile activity and as intermediaries in motor neurotransmission. The major roles of ICC have been described in the gastrointestinal tract, however, ICC-like cells (ICC-LC) can also be found in other visceral organs, including those of the lower urinary tract (LUT), where they provide similar functions, acting as electrical pacemakers and as intermediary cells involved in the modulation of neurotransmission to adjacent smooth muscle cells. The physiological functions of ICC-LC, in particular their role as pacemakers, relies on their ability to generate transient and propagating intracellular Ca2+ events. The role of ICC-LC as pacemakers and neuromodulators in the LUT is increasingly apparent and the study of their intracellular Ca2+ dynamics will provide a better understanding of their role in LUT excitability.

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Figure 1: Syncytium of nerves, ICC-LC, PDGFRα+ cells and smooth muscle cells in the bladder detrusor.
Figure 2: Spontaneous Ca2+ waves in urethral ICC-LC.
Figure 3: ICC-LC mechanism of Ca2+ wave propagation.
Figure 4: Urethral ICC-LC pacemaking mechanism.
Figure 5: Schematic of prostate ICC-LC pacemaking mechanism.

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Acknowledgements

This work was supported by grant support: R01 DK098388 to S.D.K. and R01 DK-57236 & P01 DK41315 to S.M.W.

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Authors and Affiliations

  1. Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, 89557, NV, USA

    Bernard T. Drumm, Sang Don Koh & Sean M. Ward

  2. Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, 27106, NC, USA

    Karl-Erik Andersson

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  1. Bernard T. Drumm
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  2. Sang Don Koh
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Contributions

B.T.D. and S.M.W. researched data for the article and wrote the manuscript. B.T.D., K.-E.A. and S.M.W. made substantial contributions to discussion of content. All authors reviewed and edited the manuscript before submission.

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Correspondence to Bernard T. Drumm.

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Drumm, B., Koh, S., Andersson, KE. et al. Calcium signalling in Cajal-like interstitial cells of the lower urinary tract. Nat Rev Urol 11, 555–564 (2014). https://doi.org/10.1038/nrurol.2014.241

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