Expression of the cardiac ryanodine receptor in the compensated phase of hypertrophy in rat heart.
OBJECTIVE
Abnormal calcium handling is a general feature of cardiac hypertrophy and alteration in the expression of SR proteins has been suggested to be involved in this alteration. To determine the expression of the cardiac ryanodine receptor (Ry2) gene during compensatory hypertrophy, we studied the mRNA and protein accumulation in left ventricles from rats with 30 to 100% hypertrophy.


METHODS
Cardiac hypertrophy was obtained after 1 month of aortic constriction. Ry2 mRNA was analyzed by RNase protection assay, Northern and slot blots, and Ry2 protein by high-affinity [3H]ryanodine binding and Western blot.


RESULTS
We demonstrate that: (1) the cardiac Ry2 mRNA concentration is decreased by 50% in severe hypertrophy; (2) both the density of the high-affinity sites and the Ry2 protein level are decreased by 25%; (3) the decrease in the mRNA and protein levels and the number of high-affinity sites are highly correlated to the severity of hypertrophy.


CONCLUSIONS
Our results suggest that, as for SR Ca(2+)-ATPase, there is either a downregulation 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 slowing the Ca2+ movements.
Rannou
F
F
INSERM, U-127, Université Denis Diderot, Hôpital Lariboisière, Paris, France.
Dambrin
G
G
Marty
I
I
Carré
F
F
Trouvé
P
P
Lompré
A M
AM
Charlemagne
D
D
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D015220:Calcium Channels / Q000032:analysis* / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism*; D006352:Heart Ventricles / Q000737:chemistry; D008297:Male; D009124:Muscle Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel
D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel