Relation between cytosolic free calcium and respiratory rates in cardiac myocytes.
Rates of O2 uptake of isolated rat cardiac myocytes were determined as a function of cytosolic free Ca2+ concentration ([Ca2+]c) that was estimated from intracellular quin2 fluorescence. [Ca2+]c was increased by depolarization with K+ or veratridine. In each case, there was a correlation between increase in [Ca2+]c and stimulation of O2 uptake. Apparent exception seen on raising K+ were resolved on the of an effect of osmolality on O2 uptake rates. Increase in O2 uptake and [Ca2+]c by veratridine was sensitive to variation of extracellular Na+, Ca2+, and pH in a way that suggests a major involvement of the Na+-Ca2+ exchange: partial inhibition by 2.7 microM verapamil and total inhibition by 30 microM 3',4'-dichlorobenzamil were consistent with this conclusion. Attempts were made to assess the quantitative significance of direct activation of respiration by Ca2+ at the level of mitochondrial dehydrogenases vs. an indirect mechanism involving increased ADP generation. Ruthenium red, which blocks the former process but not the latter, gave a small decrease in O2 uptake rates. However, activation of oxidative phosphorylation by ADP was predominant under these conditions of profound and sustained depolarization, based on a lowered mitochondrial NADH content in response to veratridine.
Moreno-Sánchez
R
R
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland 21224.
Hansford
R G
RG
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D012402:Rotenone; D009243:NAD; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D009249:NADP; D000968:Antimycin A; D014701:Veratridine; D012964:Sodium; D014700:Verapamil; D011188:Potassium; D002118:Calcium