Methods and Results-Whole-heart histology and electrophysiology in isolated cardiomyocytes identified calcium channel overexpression in the hearts of transgenic mice. Calcium-channel density was increased in 2-, 4-, and 8-month-old transgenic cardiomyocytes. Ventricular fibrosis, damage, and remodeling became more pronounced as the transgenic mice aged. Apoptosis was also present in transgenic hearts at 8 months of age. Increased protein kinase C alpha activation was elevated before the development of hypertrophy and failure.

Conclusions-Transgenic mice developed hypertrophy and severe cardiomyopathy as a function of age, thus confirming that changes in channel density are sufficient to induce disease. The small, sustained increase in the ingress of Ca2+ through the calcium channel elevated protein kinase C alpha before the development of hypertrophy, suggesting that protein kinase C alpha plays an important role in triggering hypertrophy.