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Caveolin-3 (Cav-3) is a protein that has been implicated in t-tubule formation and function in cardiac ventricular myocytes. In cardiac hypertrophy and failure, Cav-3 expression decreases, t-tubule structure is disrupted and excitation-contraction coupling (ECC) is impaired. However, the extent to which the decrease in Cav-3 expression underlies these changes is unclear. We therefore investigated the structure and function of myocytes isolated from the hearts of Cav-3 KO mice. These mice showed cardiac dilatation and decreased ejection fraction in vivo, compared to WT controls. Isolated KO myocytes showed cellular hypertrophy and altered t-tubule structure, and decreased L-type Ca channel (LTCC) current (ICa) density. This decrease in density occurred predominantly in the t-tubules, with no change in total ICa, and was therefore a consequence of the increase in membrane area. Cav-3 KO had no effect on LTCC expression, and C3SD peptide, which mimics the scaffolding domain of Cav-3, had no effect on ICa in KO myocytes. However, inhibiting protein kinase A using H-89 decreased ICa at the surface and t-tubule membranes in both KO and WT myocytes. Cav-3 KO had no significant effect on INCX or Ca release. These data suggest that Cav-3 KO causes cellular hypertrophy thereby decreasing t-tubular ICa density.
|Number of pages||11|
|Journal||AJP - Heart and Circulatory Physiology|
|Early online date||20 Jul 2018|
|Publication status||Published - 1 Nov 2018|
- calcium current
- calcium transient
- calcium release
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- 1 Finished
Role of cardiac t-tubules in Ca regulation and arrhythmogenesis
Bedford, A. M.
1/01/15 → 31/12/17
Dr Andrew F James
- School of Physiology, Pharmacology & Neuroscience - Senior Lecturer