In this study, we test the hypothesisthat in newborn hearts (as in adults) hypoxia and acidificationstimulate increased Na
+ uptake, in part via pH-regulatoryNa
+/H
+ exchange. Resulting increases inintracellular Na
+ (Na
i) alter the force drivingthe Na
+/Ca
2+ exchanger and lead to increasedintracellular Ca
2+. NMR spectroscopy measuredNa
i and cytosolic Ca
2+ concentration([Ca
2+]
i) and pH (pH
i) inisolated, Langendorff-perfused 4- to 7-day-old rabbit hearts. AfterNa
+/K
+ ATPase inhibition, hypoxic hearts gainedNa
+, whereas normoxic controls did not [19 ± 3.4 to139 ± 14.6 vs. 22 ± 1.9 to 22 ± 2.5 (SE) meq/kg drywt, respectively]. In normoxic hearts acidified using theNH
4Cl 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 inadults (
P < 0.05). Increases in Na
i and[Ca]
i were inhibited by theNa
+/H
+ exchange inhibitormethylisobutylamiloride (MIA, 40 µM;
P < 0.05), aswell as by increasing perfusate osmolarity (+30 mosM) immediately before and during hypoxia (
P < 0.05). The data supportthe hypothesis that in newborn hearts, like adults, increases inNa
i and [Ca]
i during hypoxia and afternormoxic acidification are in large part the result of increased uptakevia Na
+/H
+ and Na
+/Ca
2+exchange, respectively. However, for similar hypoxia and acidification protocols, this increase in [Ca]
i is less in newborn thanadult hearts.
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