Interstitial cell of Cajal-like cells (ICC-LC) exhibit dynamic spontaneous activity but are not functionally innervated in mouse urethra.

Autor: Gupta N; Smooth Muscle Research Centre, Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Co. Louth, Ireland., Baker SA; Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA., Sanders KM; Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA., Griffin CS; Smooth Muscle Research Centre, Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Co. Louth, Ireland., Sergeant GP; Smooth Muscle Research Centre, Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Co. Louth, Ireland., Hollywood MA; Smooth Muscle Research Centre, Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Co. Louth, Ireland., Thornbury KD; Smooth Muscle Research Centre, Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Co. Louth, Ireland., Drumm BT; Smooth Muscle Research Centre, Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Co. Louth, Ireland; Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA. Electronic address: bernard.drumm@dkit.ie.
Jazyk: angličtina
Zdroj: Cell calcium [Cell Calcium] 2024 Nov; Vol. 123, pp. 102931. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.1016/j.ceca.2024.102931
Abstrakt: Urethral smooth muscle cells (USMC) contract to occlude the internal urethral sphincter during bladder filling. Interstitial cells also exist in urethral smooth muscles and are hypothesized to influence USMC behaviours and neural responses. These cells are similar to Kit + interstitial cells of Cajal (ICC), which are gastrointestinal pacemakers and neuroeffectors. Isolated urethral ICC-like cells (ICC-LC) exhibit spontaneous intracellular Ca 2+ signalling behaviours that suggest these cells may serve as pacemakers or neuromodulators similar to ICC in the gut, although observation and direct stimulation of ICC-LC within intact urethral tissues is lacking. We used mice with cell-specific expression of the Ca 2+ indicator, GCaMP6f, driven off the endogenous promoter for Kit (Kit-GCaMP6f mice) to identify ICC-LC in situ within urethra muscles and to characterize spontaneous and nerve-evoked Ca 2+ signalling. ICC-LC generated Ca 2+ waves spontaneously that propagated on average 40.1 ± 0.7 μm, with varying amplitudes, durations, and spatial spread. These events originated from multiple firing sites in cells and the activity between sites was not coordinated. ICC-LC in urethra formed clusters but not interconnected networks. No evidence for entrainment of Ca 2+ signalling between ICC-LC was obtained. Ca 2+ events in ICC-LC were unaffected by nifedipine but were abolished by cyclopiazonic acid and decreased by an antagonist of Orai Ca 2+ channels (GSK-7975A). Phenylephrine increased Ca 2+ event frequency but a nitric oxide donor (DEA-NONOate) had no effect. Electrical field stimulation (EFS, 10 Hz) of intrinsic nerves, which evoked contractions of urethral rings and increased Ca 2+ event firing in USMC, failed to evoke responses in ICC-LC. Our data suggest that urethral ICC-LC are spontaneously active but are not regulated by autonomic neurons.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest in relation to this work.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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