Developmental differences in cytosolic calcium accumulation associated with global ischemia: evidence for differential intracellular calcium channel receptor activity.
BACKGROUND
Cytosolic calcium ([Ca2+]i) accumulation during global ischemia is increased 30% more in the aged compared with the mature heart and is associated with decreased functional recovery. Recently, we have shown that [Ca2+]i accumulation occurs via the ryanodinc sensitive (RyR) and the inositol (1,4,5) triphosphate calcium channels (IP3) but not the Na+/Ca2+ exchanger in both the mature and aged heart, suggesting that the increase in [Ca2+]i accumulation in the aged heart may result from either alteration of intracellular Ca2+ channel receptor activity or abundance.


METHODS
[3H]-Ryanodine and [3H]-Inositol (1,4,5) triphosphate binding was determined in mature (MAT; 15 to 20 weeks) and aged (AGE; >130 weeks) rabbit hearts perfused for 60 minutes (control) or perfused for 30 minutes then subjected to 30 minutes of global ischemia (global ischemia).


RESULTS
RyR and IP3R activities in control were decreased significantly (P<.05) in aged compared with mature hearts. Global ischemia significantly decreased RyR activity in MAT but not in AGE. IP3R was significantly increased (P<.05) during global ischemia in AGE but not in MAT. Northern and Western blot analysis indicated that there were no differences in RyR or IP3R mRNA or protein levels between MAT and AGE.


CONCLUSIONS
Aging alters intracellular Ca2+ channel activity. Ca2+ channel activity is decreased during global ischemia in mature but increased in the aged heart resulting in increased [Ca2+]i accumulation. Differences in RyR and IP3R activities were shown not to be the result of a decrease in receptor mRNA or protein levels in the aged compared with the mature heart.
Matsuda
H
H
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass, USA.
McCully
J D
JD
Levitsky
S
S
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000032:analysis*; D003600:Cytosol / Q000378:metabolism; D006439:Hemodynamics; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium