title: Nifedipine does not alter the increased cystolic free magnesium during inhibition of mitochondrial function in isolated cardiac myocytes.
abstract: 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.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: S W
authors.initials: SW
authors.lastname: Rabkin
authors.forename: N
authors.initials: N
authors.lastname: Freestone
authors.forename: G A
authors.initials: GA
authors.lastname: Quamme
mesh_terms: 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*
chemical_list: D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D008274:Magnesium; D009543:Nifedipine; D002118:Calcium