| First Author | Comerma-Steffensen S | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 3839 |
| PubMed ID | 28630432 | Mgi Jnum | J:270984 |
| Mgi Id | MGI:6278575 | Doi | 10.1038/s41598-017-04188-5 |
| Citation | Comerma-Steffensen S, et al. (2017) Down-regulation of KCa2.3 channels causes erectile dysfunction in mice. Sci Rep 7(1):3839 |
| abstractText | Modulation of endothelial calcium-activated K(+) channels has been proposed as an approach to restore arterial endothelial cell function in disease. We hypothesized that small-conductance calcium-activated K(+) channels (KCa2.3 or SK3) contributes to erectile function. The research was performed in transgenic mice with overexpression (KCa2.3 (T/T(-Dox))) or down-regulation (KCa2.3 (T/T(+Dox))) of the KCa2.3 channels and wild-type C57BL/6-mice (WT). QPCR revealed that KCa2.3 and KCa1.1 channels were the most abundant in mouse corpus cavernosum. KCa2.3 channels were found by immunoreactivity and electron microscopy in the apical-lateral membrane of endothelial cells in the corpus cavernosum. Norepinephrine contraction was enhanced in the corpus cavernosum of KCa2.3 (T/T(+Dox)) versus KCa2.3 (T/T(-Dox)) mice, while acetylcholine relaxation was only reduced at 0.3 microM and relaxations in response to the nitric oxide donor sodium nitroprusside were unaltered. An opener of KCa2 channels, NS309 induced concentration-dependent relaxations of corpus cavernosum. Mean arterial pressure was lower in KCa2.3 (T/T(-Dox)) mice compared with WT and KCa2.3 (T/T(+Dox)) mice. In anesthetized mice, cavernous nerve stimulation augmented in frequency/voltage dependent manner erectile function being lower in KCa2.3 (T/T(+Dox)) mice at low frequencies. Our findings suggest that down-regulation of KCa2.3 channels contributes to erectile dysfunction, and that pharmacological activation of KCa2.3 channels may have the potential to restore erectile function. |
