HCO3−‐Dependent Intracellular pH Regulation in the Premature Myocardium
作者:
Toshio Nakanishi,
Hong Gu,
Masashi Seguchi,
Edward Cragoe,
Kazuo Momma,
期刊:
Circulation Research
(OVID Available online 1992)
卷期:
Volume 71,
issue 6
页码: 1314-1323
ISSN:0009-7330
年代: 1992
出版商: OVID
关键词: intracellular pH;adult myocytes;newborn myocytes;Na+-H+ exchange;HCO3−-Cl−exchange
数据来源: OVID
摘要:
This study investigated developmental changes in Na+-H+ exchange and HCO3−-Cl−exchange activities in newborn and adult rabbit hearts. pHiwas measured using the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in isolated myocytes. Myocardial mechanical function was measured in the isolated ventricular preparation. Intracellular acidosis with normal pH. was induced by an NH4Cl (10 mM) prepulse technique. Upon removal of NH4Cl, pHifell transiently and then recovered toward the control level. In the HCO3-/CO2-buffered solution, the rate of recovery of pH;in the newborn was greater than in the adult. In the HCO3-/CO2-buffered solution, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of Na+-H+ exchange, inhibited the recovery of pHicompletely in the adult. In the newborn, however, significant recovery of pHiwas observed in the presence of EIPA. In the presence of both EIPA and 4-acetamido-4'-isothiocyanatostilbene-2',2'-disulfonic acid (SITS), an inhibitor of HCO3-Cl exchange, the recovery of pHiwas not observed in the two age groups. In the HEPES-buffered solution that did not contain HCO3-/CO2, the rate of recovery of pHiafter NH4Cl removal was similar in the two age groups. In the HEPES-buffered solution, the recovery of pHiwas completely inhibited by EIPA in the two age groups. In the presence of EIPA in the HCO3/CO2-buffered solution, contractile function decreased during acidosis after NH4Cl removal and did not recover in the adult. In the newborn, significant recovery of contractile function was observed after NH4Cl removal in the presence of EIPA. The recovery of mechanical function observed in the presence of EIPA in the newborn was inhibited by SITS. These data suggest that, although there is no developmental change in the Na+-H+ exchange activity, HCO3-Cl exchange is more active in the premature myocardium. The presence of the HCO3−-Cl- exchanger is important in maintaining myocardial contractile function during acidosis, especially when Na+-H+ exchange is inhibited and may partly explain the greater resistance of the premature myocardium to acidosis.
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