A characterization of caveolins/caveolae in cardiac and smooth muscle tissues
Woodman, Scott E.
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To better understand the role of caveola/caveolins in electrically responsive cells we examined cardiac muscle and urogenital smooth muscle tissues in mice genetically engineered to be caveolin deficient.;Only Cav-3 is expressed in adult mouse cardiac myocytes. Caveolin-3 knock-out (Cav-3 KO) mouse hearts fail to express the Cav-3 protein and Cav-3 KO cardiac myocytes do not form caveolae. These hearts still express Cav-1 and Cav-2, corresponding to the caveolae formation in cardiac endothelium. Cav-3 KO hearts are hypertrophy and display a reduction in fractional shortening by gated cardiac MRI and transthoracic echocardiography. Histological analysis also show Cav-3 KO hearts to be hypertrophic with an increase in cellular infiltrates. Although the expression and membrane association of dystophin-glycoprotein complex (DGC) proteins remain unchanged, a DGC marker, alpha-sarcoglycan, is excluded from lipid raft/caveolar domains. Mitogen-Activated Protein Kinase activity is increased in Cav-3 KO hearts. These results suggest that Cav-3 generated caveolae in cardiac myocytes play a role in facilitating membrane signaling.;All caveolin family members are expressed in adult mouse urinary bladder. Cav-1 KO mouse urinary bladders fail to express Cav-1, show a near complete loss of Cav-2, with no significant change in Cav-3 expression. Cav-3 KO mouse urinary bladders fail to express Cav-3, but express Cav-1 and Cav-2 in normal amounts. Caveolae formation was only reduced in Cav-1 KO mouse urinary bladders, showing Cav-1 to be the primary caveolae-forming caveolin family member. Cystometric analysis of urinary bladder function within Cav-1 KO mouse urinary bladders show higher basal, threshold, and spontaneous pressure measurements as compared to wild-type controls. Histological analysis reveals urinary bladder smooth muscle cell hypertrophy in the Cav-1 KO mouse. Cav-1 KO bladder strips have a diminished contractile response to the muscarinic agonist carbachol and KCl membrane depolarization. These results suggest that Cav-1 generated caveolae may play an important role in the facilitation of urinary bladder smooth muscle cell contraction.
- Theses and Dissertations