Age-related differences in Na+-dependent Ca2+ accumulation in rabbit hearts exposed to hypoxia and acidification

S. E. Anderson, Hong Liu, Hung S Ho, E. J. Lewis, Peter M Cala

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 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 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 inhibitormethylisobutylamiloride (MIA, 40 μM; 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number5 53-5
StatePublished - May 1 2003

Keywords

  • Intracellular Na, Ca, and pH
  • Newborn heart

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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