| First Author | Correll RN | Year | 2017 |
| Journal | Cardiovasc Res | Volume | 113 |
| Issue | 7 | Pages | 749-759 |
| PubMed ID | 28402392 | Mgi Jnum | J:263301 |
| Mgi Id | MGI:6163645 | Doi | 10.1093/cvr/cvx046 |
| Citation | Correll RN, et al. (2017) Caveolae-localized L-type Ca2+ channels do not contribute to function or hypertrophic signalling in the mouse heart. Cardiovasc Res 113(7):749-759 |
| abstractText | Aims: L-type Ca2+ channels (LTCCs) in adult cardiomyocytes are localized to t-tubules where they initiate excitation-contraction coupling. Our recent work has shown that a subpopulation of LTCCs found at the surface sarcolemma in caveolae of adult feline cardiomyocytes can also generate a Ca2+ microdomain that activates nuclear factor of activated T-cells signaling and cardiac hypertrophy, although the relevance of this paradigm to hypertrophy regulation in vivo has not been examined. Methods and results: Here we generated heart-specific transgenic mice with a putative caveolae-targeted LTCC activator protein that was ineffective in initiating or enhancing cardiac hypertrophy in vivo. We also generated transgenic mice with cardiac-specific overexpression of a putative caveolae-targeted inhibitor of LTCCs, and while this protein inhibited caveolae-localized LTCCs without effects on global Ca2+ handling, it similarly had no effect on cardiac hypertrophy in vivo. Cardiac hypertrophy was elicited by pressure overload for 2 or 12 weeks or with neurohumoral agonist infusion. Caveolae-specific LTCC activator or inhibitor transgenic mice showed no greater change in nuclear factor of activated T-cells activity after 2 weeks of pressure overload stimulation compared with control mice. Conclusion: Our results indicate that LTCCs in the caveolae microdomain do not affect cardiac function and are not necessary for the regulation of hypertrophic signaling in the adult mouse heart. |
