| First Author | Yamamura H | Year | 2013 |
| Journal | Am J Physiol Cell Physiol | Volume | 305 |
| Issue | 3 | Pages | C299-308 |
| PubMed ID | 23703524 | Mgi Jnum | J:205026 |
| Mgi Id | MGI:5543885 | Doi | 10.1152/ajpcell.00065.2013 |
| Citation | Yamamura H, et al. (2013) Overactive bladder mediated by accelerated Ca2+ influx mode of Na+/Ca2+ exchanger in smooth muscle. Am J Physiol Cell Physiol 305(3):C299-308 |
| abstractText | The Na(+)/Ca(2+) exchanger (NCX) is thought to be a key molecule in the regulation of cytosolic Ca(2+) dynamics. The relative importance of the two Ca(2+) transport modes of NCX activity leading to Ca(2+) efflux (forward) and influx (reverse) in smooth muscle, however, remains unclear. Unexpectedly, spontaneous contractions of urinary bladder smooth muscle (UBSM) were enhanced in transgenic mice overexpressing NCX1.3 (NCX1.3(tg/tg)). The enhanced activity was attenuated by KB-R7943 or SN-6. Whole cell outward NCX current sensitive to KB-R7943 or Ni(2+) was readily detected in UBSM cells from NCX1.3(tg/tg) but not wild-type mice. Spontaneous Ca(2+) transients in myocytes of NCX1.3(tg/tg) were larger and frequently resulted in propagating events and global elevations in cytosolic Ca(2+) concentration. Significantly, NCX1.3(tg/tg) mice exhibited a pattern of more frequent urination of smaller volumes and this phenotype was reversed by oral administration of KB-R7943. On the other hand, KB-R7943 did not improve it in KB-R7943-insensitive (G833C-)NCX1.3(tg/tg) mice. We conclude that NCX1.3 overexpression is associated with abnormal urination owing to enhanced Ca(2+) influx via reverse mode NCX leading to prolonged, propagating spontaneous Ca(2+) release events and a potentiation of spontaneous UBSM contraction. These findings suggest the possibility that NCX is a candidate molecular target for overactive bladder therapy. |
