Other
12 Authors
- Kunz S,
- Matthaeus C,
- Tsvetkov D,
- Cui Y,
- Zhong C,
- Kaßmann M,
- Daumke O,
- Gollasch M,
- Zhu S,
- Huang Y,
- Xie Y,
- Fan G
| First Author | Fan G | Year | 2020 |
| Journal | Aging Cell | Volume | 19 |
| Issue | 4 | Pages | e13134 |
| PubMed ID | 32187825 | Mgi Jnum | J:287521 |
| Mgi Id | MGI:6414683 | Doi | 10.1111/acel.13134 |
| Citation | Fan G, et al. (2020) Age attenuates the T-type CaV 3.2-RyR axis in vascular smooth muscle. Aging Cell 19(4):e13134 |
| abstractText | Caveolae position CaV 3.2 (T-type Ca(2+) channel encoded by the alpha-3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca(2+) influx to trigger Ca(2+) sparks and large-conductance Ca(2+) -activated K(+) channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca(2+) spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Cav 3.2 channel inhibition by Ni(2+) (50 microM) and caveolae disruption by methyl-ss-cyclodextrin or genetic abolition of Eps15 homology domain-containing protein (EHD2) inhibited Ca(2+) sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Cav 3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Cav 1.2(-/-) mice, caffeine (RyR activator) and thapsigargin (Ca(2+) transport ATPase inhibitor), we found that sufficient SR Ca(2+) load is a prerequisite for the CaV 3.2-RyR axis to generate Ca(2+) sparks. We identified a fraction of Ca(2+) sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd(3+) (100 microM), but insensitive to CaV 1.2 and CaV 3.2 channel blockade. Our data demonstrate that the VSMC CaV 3.2-RyR axis is down-regulated by aging. This defective CaV 3.2-RyR coupling is counterbalanced by a Gd(3+) sensitive Ca(2+) pathway providing compensatory Ca(2+) influx for triggering Ca(2+) sparks in aged VSMCs. |
