Platelet-derived growth factor receptor-α (PDGFRα) is a novel biomarker along with smooth myosin heavy chain for the pacemaker cells (previously termed 'atypical' smooth muscle cells) in the murine and cynomolgus monkey pelvis-kidney junction. r PDGFRα + cells present in adventitial and urothelial layers of murine renal pelvis do not express smooth muscle myosin heavy chain (smMHC) but are in close apposition to nerve fibres. r Most c-Kit + cells in the renal pelvis are mast cells. Mast cells (CD117 + /CD45 +) are more abundant in the proximal renal pelvis and pelvis-kidney junction regions whereas c-Kit + interstitial cells (CD117 + /CD45 −) are found predominantly in the distal renal pelvis and ureteropelvic junction. r PDGFRα + cells are distinct from c-Kit + interstitial cells. r A subset of PDGFRα + cells express the Ca 2+-activated Cl − channel, anoctamin-1, across the entire renal pelvis. r Spontaneous Ca 2+ transients were observed in c-Kit + interstitial cells, smMHC + PDGFRα cells and smMHC − PDGFRα cells using mice expressing genetically encoded Ca 2+ sensors.

The process of urine removal from the kidney occurs via the renal pelvis. The renal pelvis demarcates the beginning of the upper urinary tract and is endowed with smooth muscle cells. Along the renal pelvis, organized contraction of smooth muscle cells generates the force required to move urine boluses towards the ureters and bladder. This process is mediated by specialized pacemaker cells that are highly expressed in the proximal renal pelvis that generate spontaneous rhythmic electrical activity to drive smooth muscle depolarization. The mechanisms by which peristaltic contractions propagate from the proximal to distal renal pelvis are not fully understood. In this study, we utilized a transgenic mouse that expresses the genetically encoded Ca2+ indicator, GCaMP3, under a myosin heavy chain promotor to visualize spreading peristaltic contractions in high spatial detail. Using this approach, we discovered variable effects of L-type Ca2+ channel antagonists on contraction parameters. Inhibition of T-Type Ca2+ channels reduced the frequency and propagation distance of contractions. Similarly, antagonizing Ca2+-activated Cl− channels or altering the transmembrane Cl− gradient decreased contractile frequency and significantly inhibited peristaltic propagation. These data suggest that voltage gated Ca2+ channels are important determinants of contraction initiation and maintain the fidelity of peristalsis as the spreading contraction moves further towards the ureter. Recruitment of Ca2+-activated Cl− channels, likely Anoctamin-1, and T-Type Ca2+ channels are required for efficiently conducting the depolarizing current throughout the length of the renal pelvis. These mechanisms are necessary for the efficient removal of urine from the kidney.