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The effects of low-flow ischemia on K+ fluxes in isolated rat hearts assessed by 87Rb NMR.
- Source :
-
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 1999 Apr; Vol. 31 (4), pp. 817-26. - Publication Year :
- 1999
-
Abstract
- This study investigated whether Na+/K+ ATPase is inhibited and KATP channels activated during low flow ischemia (LFI) by monitoring Rb+ uptake and efflux from rat hearts using 87Rb NMR. In the uptake experiments, isolated Langendorff perfused hearts were exposed to Rb+-containing Krebs-Henseleit buffer (2.14 m m+3.76 m m K+) for 60 min. When Rb+ uptake started the flow of perfusate was decreased from 10 to 1 ml/min/g wet weight for 44 min and then returned to normal. The rate of Rb+ uptake and its equilibrium level decreased to 40 and 65% of the control (no ischemia) levels, respectively. Phosphocreatine and cytoplasmic [ATP]/[ADP] measured by 31P NMR decreased by half, intracellular pH (pHi) decreased to 6.8+/-0.1, and Pi increased two-fold. In wash-out experiments the hearts were pre-loaded with Rb+ for 30 min following which Rb+ wash-out was initiated. Four minutes later, flow was either decreased in the absence or presence of 10 microm 2,4-dinitrophenol (DNP), or 0.1 m m DNP was infused at normal flow for 20 min. LFI resulted in biphasic Rb+ efflux; during the initial phase, which lasted 8 min, the rate constant (kx10(3)/min) did not differ from control (43+/-3). The efflux was slightly inhibited by 5 microm glibenclamide (36+/-6) or 100 microm 5-hydroxydecanoic acid (32+/-4). In the second phase k decreased to half its initial value (18+/-2). More significant changes in energy state caused by LFI+10 microm DNP had no effect on the efflux kinetics. Similar changes in energy state induced by 0.1 m m DNP at normal flow were associated with activation of Rb+ efflux (71+/-5). DNP-stimulated Rb+ efflux was inhibited by acidosis (pHi approximately pHe = 6.7) produced with 5 m m morpholinoethane sulphonic acid (53+/-5) and by 100 microm adenosine (58+/-7). We suggest that accumulation of ischemic products such as H+and adenosine decreases activation of KATP channels in rat hearts.<br /> (Copyright 1999 Academic Press.)
- Subjects :
- 2,4-Dinitrophenol pharmacology
Adenosine Triphosphate metabolism
Animals
Coronary Circulation
Energy Metabolism
Hemodynamics
In Vitro Techniques
Ion Transport drug effects
Magnetic Resonance Spectroscopy
Male
Myocardial Ischemia physiopathology
Perfusion
Phosphocreatine metabolism
Potassium Channels metabolism
Rats
Rats, Sprague-Dawley
Rubidium Radioisotopes
Sodium-Potassium-Exchanging ATPase metabolism
Myocardial Ischemia metabolism
Potassium metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2828
- Volume :
- 31
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of molecular and cellular cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 10329209
- Full Text :
- https://doi.org/10.1006/jmcc.1998.0920