REGIONAL AND AGE-RELATED DIFFERENCES IN MESSENGER-RNA COMPOSITION OF INTRACELLULAR CA2-RELEASE CHANNELS OF RAT CARDIAC MYOCYTES()

We investigated the mRNA distribution of three different ryanodine rec eptors (RyR) and of the intracellular Ca2+-release channel/inositol 1, 4,5-trisphosphate receptor (IP3R) type 1 in the rat heart during devel opment and aging. In situ hybridization analysis shows that RyR1 mRNA is never expressed in the heart at any of the stages examined; RyR2 mR NA is; detectable in cardiomyocytes in the early embryonic stages, whe reas RyR3 mRNA accumulates in cardiomyocytes around birth. IP3R mRNA a ppears al first in the primitive atrium at embryonic day 11 and in sub sequent stages it is detectable also in a minor population of ventricu lar myocytes, which presumably correspond to conduction system precurs ors. In the adult heart, no apparent difference in hybridization signa l intensity is observed between atrial and ventricular working myocyte s either with RyR2, RyR3 or IP3R cRNA probes, except for myocytes of t he heart conduction system, which differ from working myocytes in the intensity of the hybridization signals for each probe. Additional diff erences are detected in the senescent heart with the IP3R cRNA probe, which hybridizes with atrial myocytes stronger than with ventricular o nes. RNase protection analysis confirms the temporal differences in Ry RZ and RyR3 transcript accumulation observed during heart development and reveals a significant increase of IP3R mRNA in the atrial myocardi um during aging. Thus, the composition of intracellular Ca2+-release c hannel mRNAs of the rat heart shows temporal and regional variations: such changes might reflect important differences in transcriptional re gulation of these genes among myocytes. (C) 1997 Academic Press Limite d.