Editorial Volume 12, Issue 24 pp 24476—24478

Figure 1. Main Ca²⁺ influx pathways regulating Ca²⁺-sparks in young and aged mesenteric vascular smooth muscle cells (VSMCs). Opening of clustered RyRs in the SR produces Ca²⁺-sparks that activate BK_Ca channels providing a negative feedback effect on vasoconstriction. Ca_V1.2 L-type channels contribute to global cytosolic [Ca²⁺], thereby influencing luminal SR calcium (via SERCA) and generating the majority (75%) of Ca²⁺-sparks. Caveolae position Ca_V3.2 T-type channels close to RyRs for extracellular Ca²⁺-influx to trigger (~25%) Ca²⁺-sparks. In aged mice VSMCs, this Ca_V3.2-RyR pathway is lost. Instead, a gadolinium-sensitive Ca²⁺-influx pathway triggering (20%) Ca²⁺-sparks is upregulated. Nonselective TRP channels might be involved in this pathway. BK_Ca, Ca²⁺-activated K⁺ channels; RyR2, ryanodine receptor subtype 2; SERCA, sarcoplasmic/endoplasmic calcium pump; SR, sarcoplasmic reticulum.