Pacemaker Mechanisms Driving Pyeloureteric Peristalsis: Modulatory Role of Interstitial Cells

  • Richard J. LangEmail author
  • Hikaru Hashitani
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1124)


The peristaltic pressure waves in the renal pelvis that propel urine expressed by the kidney into the ureter towards the bladder have long been considered to be ‘myogenic’, being little affected by blockers of nerve conduction or autonomic neurotransmission, but sustained by the intrinsic release of prostaglandins and sensory neurotransmitters. In uni-papilla mammals, the funnel-shaped renal pelvis consists of a lumen-forming urothelium and a stromal layer enveloped by a plexus of ‘typical’ smooth muscle cells (TSMCs), in multi-papillae kidneys a number of minor and major calyces fuse into a large renal pelvis. Electron microscopic, electrophysiological and Ca2+ imaging studies have established that the pacemaker cells driving pyeloureteric peristalsis are likely to be morphologically distinct ‘atypical’ smooth muscle cells (ASMCs) that fire Ca2+ transients and spontaneous transient depolarizations (STDs) which trigger propagating nifedipine-sensitive action potentials and Ca2+ waves in the TSMC layer. In uni-calyceal kidneys, ASMCs predominately locate on the serosal surface of the proximal renal pelvis while in multi-papillae kidneys they locate within the sub-urothelial space. ‘Fibroblast-like’ interstitial cells (ICs) located in the sub-urothelial space or adventitia are a mixed population of cells, having regional and species-dependent expression of various Cl, K+, Ca2+ and cationic channels. ICs display asynchronous Ca2+ transients that periodically synchronize into bursts that accelerate ASMC Ca2+ transient firing. This review presents current knowledge of the architecture of the proximal renal pelvis, the role Ca2+ plays in renal pelvis peristalsis and the mechanisms by which ICs may sustain/accelerate ASMC pacemaking.


Pyeloureteric peristalsis Atypical smooth muscle cells Interstitial cells Calcium imaging Calcium channels Pacemaking Upper urinary tract 



The authors acknowledge the use of the imaging facilities within the Multi-modal Australian ScienceS Imaging and Visualization Environment (MASSIVE) at the Monash University node of the National Imaging Facility.

Supplementary material

Supplementary Video 3.1

Video of the three dimensional reconstruction of the bulb region of the mouse proximal renal pelvis (Fig. 3.1c), highlighting individual cells populations (MP4 71176 kb)

Supplementary Video 3.2

Spontaneous Ca2+ signals in atypical smooth muscle cells (ASMCs) and ICs in contraction-arrested renal pelvis using Ca2+ indicators Fluo-4 and Cal 520, illustrating their differing temporal kinetics and bursting behaviour (MP4 37878 kb)


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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.School of Biomedical Sciences, Faculty of Medicine, Nursing and Health SciencesMonash UniversityClaytonAustralia
  2. 2.Department of Cell Physiology, Graduate School of Medical SciencesNagoya City UniversityNagoyaJapan

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