title: Na-H exchange in myocardium: effects of hypoxia and acidification on Na and Ca.
abstract: 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)
authors.affiliation: Department of Human Physiology, University of California, Davis 95616.
authors.forename: S E
authors.initials: SE
authors.lastname: Anderson
authors.forename: E
authors.initials: E
authors.lastname: Murphy
authors.forename: C
authors.initials: C
authors.lastname: Steenbergen
authors.forename: R E
authors.initials: RE
authors.lastname: London
authors.forename: P M
authors.initials: PM
authors.lastname: Cala
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D012964:Sodium; D002118:Calcium