Nifedipine does not alter the increased cystolic free magnesium during inhibition of mitochondrial function in isolated cardiac myocytes.
1. The objectives of this investigation were to determine the effect of inhibition of mitochondrial function on intracellular free Mg concentration, [Mg2+]i, in the heart and to determine whether the calcium channel antagonist nifedipine would alter the response. 2. Cardiac myocytes were prepared as primary cultures from 7-day-old chick embryonic hearts. [Mg2+]i was determined in single ventricular cells with mag-fura-2. 3. Inhibition of mitochondrial function with carbonyl cyanide m-chlorophenylhydrozone (CCCP, 3 microM, plus amobarbital, 3 mM, produced a cessation of cardiac contractile frequency that was reversible. This was associated with an increase in [Mg2+]i from 0.48 to 0.98 mM which returned to near basal levels with removal of the drugs. [Ca2+]i oscillations with cell contraction were diminished in the presence of CCCP plus amobarbital and returned to normal following their removal. 4. In contrast, CCCP plus iodoacetate led to increased [Mg2+]i beyond 2 mM which was associated with elevated [Ca2+]i and cell death. 5. Nifedipine did not alter the cardiac contractile response to CCCP plus amobarbital. The increment in [Mg2+]i produced by CCCP plus amobarbital was not altered by nifedipine. These data suggest that [Mg2+]i is regulated by mitochondrial metabolism and nifedipine does not alter the increase in [Mg2+]i produced by inhibition of mitochondrial function suggesting increments in [Mg2+]i were from internal sources. Nifedipine may not interfere with the potentially beneficial actions of increased [Mg2+]i.
Rabkin
S W
SW
Department of Medicine, University of British Columbia, Vancouver, Canada.
Freestone
N
N
Quamme
G A
GA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002449:Cell Aggregation / Q000502:physiology; D002642:Chick Embryo; D003600:Cytosol / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*
D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D008274:Magnesium; D009543:Nifedipine; D002118:Calcium