Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity

Ken Lee, Sang O. Park, Pil Cho Choi, Seung Bum Ryoo, Haeyeong Lee, Lauren E. Peri, Tong Zhou, Robert D. Corrigan, Andrew C. Yanez, Suk B. Moon, Brian A. Perrino, Kenton M. Sanders, Sang Don Koh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number16268
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity'. Together they form a unique fingerprint.

Cite this