TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Fan, Gang
A1  - Kaßmann, Mario
A1  - Cui, Yingqiu
A1  - Matthaeus, Claudia
A1  - Kunz, Séverine
A1  - Zhong, Cheng
A1  - Zhu, Shuai
A1  - Xie, Yu
A1  - Tsvetkov, Dmitry
A1  - Daumke, Oliver
A1  - Huang, Yu
A1  - Gollasch, Maik
T1  - Age attenuates the T‐type CaV3.2‐RyR axis in vascular smooth muscle
JF  - Aging Cell
N2  - Abstract
Caveolae position CaV3.2 (T‐type Ca2+ channel encoded by the α‐3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca2+ influx to trigger Ca2+ sparks and large‐conductance Ca2+‐activated K+ channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca2+ spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Cav3.2 channel inhibition by Ni2+ (50 µM) and caveolae disruption by methyl‐ß‐cyclodextrin or genetic abolition of Eps15 homology domain‐containing protein (EHD2) inhibited Ca2+ sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Cav3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Cav1.2−/− mice, caffeine (RyR activator) and thapsigargin (Ca2+ transport ATPase inhibitor), we found that sufficient SR Ca2+ load is a prerequisite for the CaV3.2‐RyR axis to generate Ca2+ sparks. We identified a fraction of Ca2+ sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd3+ (100 µM), but insensitive to CaV1.2 and CaV3.2 channel blockade. Our data demonstrate that the VSMC CaV3.2‐RyR axis is down‐regulated by aging. This defective CaV3.2‐RyR coupling is counterbalanced by a Gd3+ sensitive Ca2+ pathway providing compensatory Ca2+ influx for triggering Ca2+ sparks in aged VSMCs.
KW  - -
KW  - aging
KW  - calcium sparks
KW  - caveolae
KW  - ryanodine receptors
KW  - T‐type calcium channels
KW  - vascular smooth muscle
Y1  - 2020
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-41592
U6  - https://doi.org/10.1111/acel.13134
DO  - https://doi.org/10.1111/acel.13134
VL  - 19
IS  - 4
PB  - Wiley
CY  - Hoboken, New Jersey
ER  -