Na-H exchange in myocardium: effects of hypoxia and acidification on Na and Ca.
Historically, increase in cell Na content during ischemic and hypoxic episodes were thought to result from impaired ATP production causing decreased Na(+)-K(+)-ATPase activity. Here we report the results of testing the alternate hypothesis that hypoxia-induced Na uptake is 1) the result of increased entry, as opposed to decreased extrusion 2) via Na-H exchange operating in a pH regulatory capacity and that cell Ca accumulation occurs via Na-Ca exchange secondary to collapse of the Na gradient. We used 23Na-, 19F-, and 31P-nuclear magnetic resonance (NMR) to measure intracellular Na content (Nai), Ca concentration [( Ca]i), pH (pHi), and high-energy phosphates in Langendorff-perfused rabbit hearts. When the Na(+)-K(+)-ATPase was inhibited by ouabain and/or K-free perfusion, hearts subjected to hypoxia gained Na at a rate greater than 10 times that of normoxic controls [during the first 12.5 min Nai increased from 7.9 +/- 5.8 to 34.9 +/- 11.0 (SD) meq/kg dry wt compared with 11.1 +/- 16.3 to 13.6 +/- 9.0 meq/kg dry wt, respectively]. When normoxic hearts were acidified using a 20 mM NH4Cl prepulse technique, pHi rapidly fell from 7.27 +/- 0.24 to 6.63 +/- 0.12 but returned to 7.07 +/- 0.10 within 20 min, while Na uptake was similar in rate and magnitude to that observed during hypoxia (24.5 +/- 13.4 to 132.1 +/- 17.7 meq/kg dry wt). During hypoxia and after NH4Cl washout, increases in [Ca]i were similar in time course to those observed for Na.(ABSTRACT TRUNCATED AT 250 WORDS)
Anderson
S E
SE
Department of Human Physiology, University of California, Davis 95616.
Murphy
E
E
Steenbergen
C
C
London
R E
RE
Cala
P M
PM
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D012016:Reference Values; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D012964:Sodium; D002118:Calcium