Modulation of Ca2+ Activity in Cardiomyocytes through Caveolae-Gαq Interactions

Cardiomyocytes have a complex Ca2+ behavior and changes in this behavior may underlie certain disease states. Intracellular Ca2+ activity can be regulated by the phospholipase C beta-G alpha(q) pathway localized on the plasma membrane. The plasma membranes of cardiomycoytes are rich in caveolae domains organized by caveolin proteins. Caveolae may indirectly affect cell signals by entrapping and localizing specific proteins. Recently, we found that caveolin may specifically interact with activated G alpha(q), which could affect Ca2+ signals. Here, using fluorescence imaging and correlation techniques we show that G alpha(q)-G beta gamma subunits localize to caveolae in adult ventricular canine cardiomyoctyes. Carbachol stimulation releases G beta gamma subunits from caveolae with a concurrent stabilization of activated G alpha(q) by caveolin-3 (Cav3). These cells show oscillating Ca2+ waves that are not seen in neonatal cells that do not contain Cav3. Microinjection of a peptide that disrupts Cav3-G alpha(q) association, but not a control peptide, extinguishes the waves. Furthermore, these waves are unchanged with rynaodine treatment, but not seen with treatment of a phospholipase C inhibitor, implying that Cav3-G alpha(q) is responsible for this Ca2+ activity. Taken together, these studies show that caveolae play a direct and active role in regulating basal Ca2+ activity in cardiomyocytes.