| First Author | Chung WS | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 304 |
| Issue | 12 | Pages | F1428-37 |
| PubMed ID | 23552864 | Mgi Jnum | J:197376 |
| Mgi Id | MGI:5492232 | Doi | 10.1152/ajprenal.00444.2012 |
| Citation | Chung WS, et al. (2013) betaENaC is required for whole cell mechanically gated currents in renal vascular smooth muscle cells. Am J Physiol Renal Physiol 304(12):F1428-37 |
| abstractText | Myogenic constrictor responses in small renal arteries and afferent arterioles are suppressed in mice with reduced levels of beta-epithelial Na(+) channel (betaENaC(m/m)). The underlying mechanism is unclear. Decreased activity of voltage-gated calcium channels (VGCC) or mechanically gated ion channels and increased activity of large conductance calcium-activated potassium (BK) channels are a few possible mechanisms. The purpose of this study was to determine if VGCC, BK, or mechanically gated ion channel activity was altered in renal vascular smooth muscle cell (VSMC) from betaENaC(m/m) mice. To address this, we used whole cell patch-clamp electrophysiological approaches in freshly isolated renal VSMCs. Compared with betaENaC(+/+) controls, the current-voltage relationships for VGCC and BK activity are similar in betaENaC(m/m) mice. These findings suggest neither VGCC nor BK channel dysfunction accounts for reduced myogenic constriction in betaENaC(m/m) mice. We then examined mechanically gated currents using a novel in vitro assay where VSMCs are mechanically activated by stretching an underlying elastomer. We found the mechanically gated currents, predominantly carried by Na(+), are observed with less frequency (87 vs. 43%) and have smaller magnitude (-54.1 +/- 12.5 vs. -20.9 +/- 4.9 pA) in renal VSMCs from betaENaC(m/m) mice. Residual currents are expected in this model since VSMC betaENaC expression is reduced by 50%. These findings suggest betaENaC is required for normal mechanically gated currents in renal VSMCs and their disruption may account for the reduced myogenic constriction in the betaENaC(m/m) model. Our findings are consistent with the role of betaENaC as a VSMC mechanosensor and function of evolutionarily related nematode degenerin proteins. |
