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- Title
Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity.
- Authors
Lee, Ken; Park, Sang O; Choi, Pil-Cho; Ryoo, Seung-Bum; Lee, Haeyeong; Peri, Lauren E.; Zhou, Tong; Corrigan, Robert D.; Yanez, Andrew C.; Moon, Suk B.; Perrino, Brian A.; Sanders, Kenton M.; Koh, Sang Don
- Abstract
Volume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα+ cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα+ cell density was also documented. Loss of PDGFRα+ cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα+ cells is causative in the development of DO after SCI.
- Subjects
PLATELET-derived growth factor; SPINAL cord injuries; INTERSTITIAL cells; SMOOTH muscle; MUSCLE contraction
- Publication
Scientific Reports, 2021, Vol 11, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-021-95781-2