M. Jiang et al., Thyroid hormone-induced overexpression of functional ryanodine receptors in the rabbit heart, AM J P-HEAR, 278(5), 2000, pp. H1429-H1438
Citations number
45
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Modifications in the Ca2+-uptake and -release functions of the sarcoplasmic
reticulum (SR) may be a major component of the mechanisms underlying thyro
id state-dependent alterations in heart rate, myocardial contractility, and
metabolism. We investigated the influence of hyperthyroid state on the exp
ression and functional properties of the ryanodine receptor (RyR), a major
protein in the junctional SR (JSR), which mediates Ca2+ release to trigger
muscle contraction. Experiments were performed using homogenates and JSR ve
sicles derived from ventricular myocardium of euthyroid and hyperthyroid ra
bbits. Hyperthyroidism, with attendant cardiac hypertrophy: was induced by
the injection of L-thyroxine (200 mu g/kg body wt) daily for 7 days. Wester
n blotting analysis using cardiac RyR-specific antibody revealed a signific
ant increase (>50%) in the relative amount of RyR in the hyperthyroid compa
red with euthyroid rabbits. Ca2+-dependent, high-affinity [H-3]ryanodine bi
nding was also significantly greater (similar to 40%) in JSR from hyperthyr
oid rabbits. The Ca2+ sensitivity of [H-3]ryanodine binding and the dissoci
ation constant for [H-3]ryanodine did not differ significantly between euth
yroid and hyperthyroid hearts. Measurement of Ca2+-release rates from passi
vely Ca2+-preloaded JSR vesicles and assessment of the effect of RyR-Ca2+-r
elease channel (CRC) blockade on active Ca2+-uptake rates revealed signific
antly enhanced (>2-fold) CRC activity in the hyperthyroid, compared with eu
thyroid, JSR. These results demonstrate overexpression of functional RyR in
thyroid hormone-induced cardiac hypertrophy. Relative abundance of RyR may
be responsible, in part, for the changes in SR Ca2+ release, cytosolic Ca2
+ transient, and cardiac systolic function associated with thyroid hormone-
induced cardiac hypertrophy.