Cellular distribution of Ca2+ pumps and Ca2+ release channels in rat cardiac hypertrophy induced by aortic stenosis.

BACKGROUND The response of ventricular myocytes to pressure overload is heterogeneous and not spatially coordinated. We investigated whether or not the alterations in SERCA and RyR gene expression are homogeneous within the myocardium. METHODS AND RESULTS The cellular distribution of mRNAs and proteins encoding the 2 sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) isoforms (SERCA 2a and 2b) and 2 Ca2+ release channels (the ryanodine receptor, RyR, and the IP3 receptor, IP3R) were analyzed by in situ hybridization and immunofluorescence, respectively. Analyses were performed during early (1 and 5 days) and late (1 month) stages of cardiac hypertrophy induced in rat by thoracic aortic stenosis (AS). The results indicated that 1 and 5 days after AS, the cellular distribution of SERCA 2a and RyR2 mRNAs in right ventricle and atrium was similar to controls but the mRNA levels appeared to decrease in some areas of the left ventricle (LV). One month after AS, the distribution of SERCA 2a mRNA and protein became heterogeneous throughout the LV, whereas RyR2 mRNA and protein levels were decreased in a homogeneous manner. SERCA 2b, poorly expressed in both cardiomyocytes and vessels of controls, was increased 4-fold 1 month after AS in coronary arteries only. In both sham (Sh) and AS, SERCA 3 and IP3R mRNAs were mainly found in the vessels. CONCLUSIONS In severe hypertrophy, decreased accumulation of SERCA 2a was heterogeneous and not compensated by an induction of SERCA 2b in the cardiomyocytes. Decrease in RyR2 expression was more homogeneous and not compensated by an increased IP3R expression.