Caveolae position Ca
V3.2 (T‐type Ca
2+ channel encoded by the α‐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 Ca
v3.2 channel inhibition by Ni
2+ (50 µM) 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 Ca
v3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Ca
v1.2
?/? mice, caffeine (RyR activator) and thapsigargin (Ca
2+ transport ATPase inhibitor), we found that sufficient SR Ca
2+ load is a prerequisite for the Ca
V3.2‐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 µM), but insensitive to Ca
V1.2 and Ca
V3.2 channel blockade. Our data demonstrate that the VSMC Ca
V3.2‐RyR axis is down‐regulated by aging. This defective Ca
V3.2‐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.
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