Cellular damage in the rat heart caused by caffeine or dinitrophenol.
1. Langendorff-perfusion of rat hearts with either 10 mM caffeine or 1 mM 2,4-dinitrophenol (DNP) caused severe ultrastructural damage to the myofilaments and mitochondria that was similar to that found in a standard Ca(2+)-paradox. 2. This damage occurred in the presence and absence of extracellular Ca2+. 3. Creatine kinase (CK) release (indicative of sarcolemma breakdown) was not recorded unless the caffeine- or DNP-perfusion was preceded by Ca(2+)0-depletion. 4. It is concluded that: (i) the pathways leading to damage to the myofilaments and sarcolemma are independent; (ii) the CK release mechanism requires dual activation of Ca(2+)0-depletion plus a rise in [Ca2+]i; and (iii) current theories concerning the mechanisms underlying the genesis of the Ca(2+)-paradox are incorrect or incomplete.
Daniels
S
S
Department of Environmental and Evolutionary Biology, University of Liverpool, U.K.
Duncan
C J
CJ
D019297:2,4-Dinitrophenol; D000818:Animals; D002110:Caffeine / Q000633:toxicity*; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D004140:Dinitrophenols / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D004140:Dinitrophenols; D002110:Caffeine; D003402:Creatine Kinase; D019297:2,4-Dinitrophenol