| First Author | Lee H | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 5071 |
| PubMed ID | 35332235 | Mgi Jnum | J:329160 |
| Mgi Id | MGI:7259593 | Doi | 10.1038/s41598-022-09155-3 |
| Citation | Lee H, et al. (2022) Role of detrusor PDGFRalpha(+) cells in mouse model of cyclophosphamide-induced detrusor overactivity. Sci Rep 12(1):5071 |
| abstractText | Cyclophosphamide (CYP)-induced cystitis is a rodent model that shares many features common to the cystitis occurring in patients, including detrusor overactivity (DO). Platelet-derived growth factor receptor alpha positive (PDGFRalpha(+)) cells have been proposed to regulate muscle excitability in murine bladders during filling. PDGFRalpha(+) cells express small conductance Ca(2+)-activated K(+) channels (predominantly SK3) that provide stabilization of membrane potential during filling. We hypothesized that down-regulation of the regulatory functions of PDGFRalpha(+) cells and/or loss of PDGFRalpha(+) cells generates the DO in CYP-treated mice. After CYP treatment, transcripts of Pdgfralpha and Kcnn3 and PDGFRalpha and SK3 protein were reduced in detrusor muscle extracts. The distribution of PDGFRalpha(+) cells was also reduced. Inflammatory markers were increased in CYP-treated detrusor muscles. An SK channel agonist, CyPPA, increased outward current and hyperpolarization in PDGFRalpha(+) cells. This response was significantly depressed in PDGFRalpha(+) cells from CYP-treated bladders. Contractile experiments and ex vivo cystometry showed increased spontaneous contractions and transient contractions, respectively in CYP-treated bladders with a reduction of apamin sensitivity, that could be attributable to the reduction in the SK conductance expressed by PDGFRalpha(+) cells. In summary, PDGFRalpha(+) cells were reduced and the SK3 conductance was downregulated in CYP-treated bladders. These changes are consistent with the development of DO after CYP treatment. |
