title: Modulation of Ca²+ activity in cardiomyocytes through caveolae-Gαq interactions.
abstract: Cardiomyocytes have a complex Ca(2+) behavior and changes in this behavior may underlie certain disease states. Intracellular Ca(2+) activity can be regulated by the phospholipase Cβ-Gα(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 Gα(q), which could affect Ca(2+) signals. Here, using fluorescence imaging and correlation techniques we show that Gα(q)-Gβγ subunits localize to caveolae in adult ventricular canine cardiomyoctyes. Carbachol stimulation releases Gβγ subunits from caveolae with a concurrent stabilization of activated Gα(q) by caveolin-3 (Cav3). These cells show oscillating Ca(2+) waves that are not seen in neonatal cells that do not contain Cav3. Microinjection of a peptide that disrupts Cav3-Gα(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-Gα(q) is responsible for this Ca(2+) activity. Taken together, these studies show that caveolae play a direct and active role in regulating basal Ca(2+) activity in cardiomyocytes.
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Guo
authors.forename: Urszula
authors.initials: U
authors.lastname: Golebiewska
authors.forename: Suzanne
authors.initials: S
authors.lastname: Scarlata
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D021941:Caveolae / Q000378:metabolism*; D051244:Caveolin 3 / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D005455:Fluorescent Antibody Technique; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D051244:Caveolin 3; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D010455:Peptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D002217:Carbachol; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium