isolating-imaging-live-intact-pacemaker-regions-mouse-renal-pelvis

Isolating and Imaging Live, Intact Pacemaker Regions of Mouse Renal Pelvis by Vibratome Sectioning

The renal pelvis (RP) is a funnel-shaped, smooth muscle structure that facilitates normal urine transport from the kidney to the ureter by regular, ...

University of Nevada, Reno School of Medicine

University of California School of Medicine

Electrical pacemaking in gastrointestinal muscles is generated by specialized interstitial cells of Cajal that produce the patterns of contractions required for peristalsis and segmentation in the gut. The calcium-activated chloride conductance anoctamin-1 (Ano1) has been shown to be responsible for the generation of pacemaker activity in GI muscles, but this conclusion is established from studies of juvenile animals in which effects of reduced Ano1 on gastric emptying and motor patterns could not be evaluated. Knocking down Ano1 expression using Cre/LoxP technology caused dramatic changes in in gastric motor activity, with disrupted slow waves, abnormal phasic contractions and delayed gastric emptying; modest changes were noted in the small intestine. Comparison of the effects of Ano1 antagonists on muscles from juvenile and adult small intestinal muscles suggests that conductances in addition to Ano1 may develop with age and contribute to pacemaker activity.

Differential sensitivity of gastric and small intestinal muscles to inducible knockdown of anoctamin 1 and the effects on gastrointestinal motility.

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. 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. 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. PDGFRα cells are distinct from c-Kit interstitial cells. A subset of PDGFRα cells express the Ca -activated Cl channel, anoctamin-1, across the entire renal pelvis. Spontaneous Ca transients were observed in c-Kit interstitial cells, smMHC PDGFRα cells and smMHC PDGFRα cells using mice expressing genetically encoded Ca sensors.

Article	Year
Differential sensitivity of gastric and small intestinal muscles to inducible knockdown of anoctamin 1 and the effects on gastrointestinal motility. The Journal of physiology\| PubMed ID: 30843201	2019
Identification and classification of interstitial cells in the mouse renal pelvis. The Journal of physiology\| PubMed ID: 32415739	2020

Nathan Grainger

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