EXPRESSION OF THE CARDIAC RYANODINE RECEPTOR IN THE COMPENSATED PHASEOF HYPERTROPHY IN RAT-HEART

Objectives: Abnormal calcium handing is a general Feature of cardiac h ypertrophy and alteration in the expression of SR proteins has been su ggested to be involved in this alteration. To determine the expression of the cardiac ryanodine receptor (Ry2) gent during compensatory hype rtrophy, we studied the mRNA and protein accumulation in left ventricl es from rats with 30 to 100% hypertrophy. Methods: Cardiac hypertrophy was obtained after 1 month of aortic constriction. Ry2 mRNA was analy zed by RNase protection assay, Northern rind slot blots, and Ry2, prot ein by high-affinity [H-3]ryanodine binding and Western blot. Results: We demonstrate that: (1) the cardiac Ry2 mRNA concentration is decrea sed by 50% in severe hypertrophy (2) both the density of the high-affi nity sites and the Ry2 protein level are decreased by 25%: (3) the dec rease in the mRNA and protein levels and the number of high-affinity s ites are highly correlated to the severity of hypertrophy. Conclusion: Our results suggest that, as for SR Ca2+-ATPase, there is either a do wnregulation or a lack of upregulation of the gene coding for the Ry2 in compensatory hypertrophy. The decreased density of Ry2 may alter SR Ca2+ transport and contribute to the impaired Ca2+ handling by slowin g the Ca2+ movements.