| First Author | Lee H | Year | 2013 |
| Journal | J Physiol | Volume | 591 |
| Issue | 2 | Pages | 503-13 |
| PubMed ID | 23148317 | Mgi Jnum | J:205091 |
| Mgi Id | MGI:5543999 | Doi | 10.1113/jphysiol.2012.241505 |
| Citation | Lee H, et al. (2013) Functional expression of SK channels in murine detrusor PDGFR+ cells. J Physiol 591(Pt 2):503-13 |
| abstractText | We sought to characterize molecular expression and ionic conductances in a novel population of interstitial cells (PDGFRalpha(+) cells) in murine bladder to determine how these cells might participate in regulation of detrusor excitability. PDGFRalpha(+) cells and smooth muscle cells (SMCs) were isolated from detrusor muscles of PDGFRalpha(+)/eGFP and smMHC/Cre/eGFP mice and sorted by FACS. PDGFRalpha(+) cells were highly enriched in Pdgfra (12 fold vs. unsorted cell) and minimally positive for Mhc (SMC marker), Kit (ICC marker) and Pgp9.5 (neuronal marker). SK3 was dominantly expressed in PDGFRalpha(+) cells in comparison to SMCs. alphaSlo (BK marker) was more highly expressed in SMCs. SK3 protein was observed in PDGFRalpha(+) cells by immunohistochemistry but could not be resolved in SMCs. Depolarization evoked voltage-dependent Ca(2+) currents in SMCs, but inward current conductances were not activated in PDGFRalpha(+) cells under the same conditions. PDGFRalpha(+) cells displayed spontaneous transient outward currents (STOCs) at potentials positive to -60 mV that were inhibited by apamin. SK channel modulators, CyPPA and SKA-31, induced significant hyperpolarization of PDGFRalpha(+) cells and activated SK currents under voltage clamp. Similar responses were not resolved in SMCs at physiological potentials. Single channel measurements confirmed the presence of functional SK3 channels (i.e. single channel conductance of 10 pS and sensitivity to intracellular Ca(2+)) in PDGFRalpha(+) cells. The apamin-sensitive stabilizing factor regulating detrusor excitability is likely to be due to the expression of SK3 channels in PDGFRalpha(+) cells because SK agonists failed to elicit resolvable currents and hyperpolarization in SMCs at physiological potentials. |
