Interstitial cell modulation of pyeloureteric peristalsis in the mouse renal pelvis examined using FIBSEM tomography and calcium indicators.
Pflugers Arch
; 469(5-6): 797-813, 2017 06.
Article
in En
| MEDLINE
| ID: mdl-28054154
ABSTRACT
Typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) and interstitial cells (ICs) within the pacemaker region of the mouse renal pelvis were examined using focused ion beam scanning electron (FIB SEM) tomography, immunohistochemistry and Ca2+ imaging. Individual cells within 500-900 electron micrograph stacks were volume rendered and associations with their neighbours established. 'Ribbon-shaped', Ano1 Cl- channel immuno-reactive ICs were present in the adventitia and the sub-urothelial space adjacent to the TSMC layer. ICs in the proximal renal pelvis were immuno-reactive to antibodies for CaV3.1 and hyperpolarization-activated cation nucleotide-gated isoform 3 (HCN3) channel sub-units, while basal-epithelial cells (BECs) were intensely immuno-reactive to Kv7.5 channel antibodies. Adventitial to the TSMC layer, ASMCs formed close appositions with TSMCs and ICs. The T-type Ca2+channel blocker, Ni2+ (10-200 µM), reduced the frequency while the L-type Ca2+ channel blocker (1 µM nifedipine) reduced the amplitude of propagating Ca2+ waves and contractions in the TSMC layer. Upon complete suppression of Ca2+ entry through TSMC Ca2+ channels, ASMCs displayed high-frequency (6 min-1) Ca2+ transients, and ICs distributed into two populations of cells firing at 1 and 3 min-1, respectively. IC Ca2+ transients periodically (every 3-5 min-1) summed into bursts which doubled the frequency of ASMC Ca2+ transient firing. Synchronized IC bursting and the acceleration of ASMC firing were inhibited upon blockade of HCN channels with ZD7288 or cell-to-cell coupling with carbenoxolone. While ASMCs appear to be the primary pacemaker driving pyeloureteric peristalsis, it was concluded that sub-urothelial HCN3(+), CaV3.1(+) ICs can accelerate ASMC Ca2+ signalling.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peristalsis
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Urinary Tract Physiological Phenomena
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Calcium Signaling
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Myocytes, Smooth Muscle
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Interstitial Cells of Cajal
Limits:
Animals
Language:
En
Journal:
Pflugers Arch
Year:
2017
Document type:
Article
Affiliation country: