Pacemaker Mechanisms Driving Pyeloureteric Peristalsis: Modulatory Role of Interstitial Cells

Abstract

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.