Age-related differences in Na -dependent Ca accumulation in rabbit hearts exposed to hypoxia and acidification

Anderson, S. E., H. Liu, H. S. Ho, E. J. Lewis, and P. M. Cala. Age-related differences in Na -dependent Ca2 accumulation in rabbit hearts exposed to hypoxia and acidification. Am J Physiol Cell Physiol 284: C1123–C1132, 2003. First published January 8, 2002; 10.1152/ajpcell.00148. 2002.—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 (Nai) alter the force driving the Na /Ca2 exchanger and lead to increased intracellular Ca2 . NMR spectroscopy measured Nai and cytosolic Ca2 concentration ([Ca2 ]i) and pH (pHi) in isolated, Langendorff-perfused 4to 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 NH4Cl prepulse, pHi fell rapidly and recovered, whereas Nai 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 Nai and [Ca]i were inhibited by the Na /H exchange inhibitor methylisobutylamiloride (MIA, 40 M; 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 Nai and [Ca]i during hypoxia and after normoxic acidification are in large part the result of increased uptake via Na /H and Na /Ca2 exchange, respectively. However, for similar hypoxia and acidification protocols, this increase in [Ca]i is less in newborn than adult hearts.