Changes in cytosolic Ca²⁺ are involved in various biological responses such as neurotransmission, muscle contraction, and hormone secretion. Therefore, Ca²⁺ channels and their downstream molecules make supramolecular complexes to activate specific signal pathways. We have shown that caveolin (cav)-1, an essential component of caveolae, and junctophilin (JP)-2, a protein that bridges the plasma membrane and sarcoplasmic reticulum (SR), accumulate Cav1.2 voltage dependent Ca²⁺ channels, large conductance Ca²⁺-activated K⁺ (BK) channels and ryanodine receptors within caveolae-SR junctions. This molecular complex supports an effective conversion of Ca²⁺ signals to membrane hyperpolarization by the activation of BK channels and thus, control vascular tone. In addition, we have recently revealed that the activation of a complex of Cav1.2, Ca²⁺/calmodulin-dependent kinase kinase (CaMKK)-2 and CaMK1a localized in caveolae causes transcription of pro-inflammatory genes, which promotes macrophage recruitments to the adventitia and vascular remodeling. In summary, the caveola-based supramolecular complexes convert Ca²⁺ signals to the changes in membrane potential and gene transcription, which is involved in the regulation of vascular tone and the adaptation to increased circumferential stretch, respectively.