Age-related differences in Na+-dependent Ca2+ accumulation in rabbit hearts exposed to hypoxia and acidification.
In this study, we test the hypothesis that in newborn hearts (as in adults) hypoxia and acidification stimulate increased Na(+) uptake, in part via pH-regulatory Na(+)/H(+) exchange. Resulting increases in intracellular Na(+) (Na(i)) alter the force driving the Na(+)/Ca(2+) exchanger and lead to increased intracellular Ca(2+). NMR spectroscopy measured Na(i) and cytosolic Ca(2+) concentration ([Ca(2+)](i)) and pH (pH(i)) in isolated, Langendorff-perfused 4- to 7-day-old rabbit hearts. After Na(+)/K(+) ATPase inhibition, hypoxic hearts gained Na(+), whereas normoxic controls did not [19 +/- 3.4 to 139 +/- 14.6 vs. 22 +/- 1.9 to 22 +/- 2.5 (SE) meq/kg dry wt, respectively]. In normoxic hearts acidified using the NH(4)Cl prepulse, pH(i) fell rapidly and recovered, whereas Na(i) rose from 31 +/- 18.2 to 117.7 +/- 20.5 meq/kg dry wt. Both protocols caused increases in [Ca](i); however, [Ca](i) increased less in newborn hearts than in adults (P < 0.05). Increases in Na(i) and [Ca](i) were inhibited by the Na(+)/H(+) exchange inhibitor methylisobutylamiloride (MIA, 40 microM; P < 0.05), as well as by increasing perfusate osmolarity (+30 mosM) immediately before and during hypoxia (P < 0.05). The data support the hypothesis that in newborn hearts, like adults, increases in Na(i) and [Ca](i) during hypoxia and after normoxic acidification are in large part the result of increased uptake via Na(+)/H(+) and Na(+)/Ca(2+) exchange, respectively. However, for similar hypoxia and acidification protocols, this increase in [Ca](i) is less in newborn than adult hearts.
Anderson
S E
SE
Department of Human Physiology, University of California, Davis, California 95616-8644, USA. seanderson@ucdavis.edu
Liu
H
H
Ho
H S
HS
Lewis
E J
EJ
Cala
P M
PM
D000143:Acids / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D006982:Hypertonic Solutions / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010710:Phosphates / Q000378:metabolism; D011522:Protons; D011817:Rabbits; D012964:Sodium / Q000037:antagonists & inhibitors / Q000502:physiology*; D014655:Vascular Resistance
D000143:Acids; D006982:Hypertonic Solutions; D010710:Phosphates; D011522:Protons; D012964:Sodium; D002118:Calcium