Caffeine alters cardiac myofilament activity and regulation independently of Ca2+ binding to troponin C.
We investigated the mechanism by which caffeine influences myofilament responsiveness to Ca2+ by measuring isometric force, Ca2+ binding, and ATPase activity of dog cardiac myofilament proteins. Caffeine (20 mM) increased submaximal and depressed maximal force in skinned fiber bundles. Although the Ca2+ sensitivity of myofilament activity was increased by caffeine, there was no effect on Ca2+ binding to troponin C (TnC) in skinned fiber bundles. To determine if caffeine altered actin-myosin interaction or affected myosin directly, myofibrillar, actomyosin, and myosin ATPase activities were measured. Maximal Ca(2+)-activated myofibrillar Mg(2+)-ATPase activity was depressed by 20 mM caffeine, whereas submaximal Mg(2+)-ATPase activities were not changed. Actomyosin Mg(2+)-ATPase activity was significantly depressed by caffeine concentrations > or = 15 mM. Myosin Ca(2+)-ATPase activity was depressed by caffeine, whereas Mg(2+)-ATPase and K(EDTA)-ATPase activities were not affected. These data suggest that caffeine affects myofilament function via a mechanism that is independent of TnC-Ca2+ binding but that may involve direct effects on actin-cross-bridge interaction.
Powers
F M
FM
Department of Physiology and Biophysics, University of Illinois at Chicago 60618.
Solaro
R J
RJ
D000205:Actomyosin / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004285:Dogs; D004533:Egtazic Acid / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects; D009210:Myofibrils / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D011485:Protein Binding; D014336:Troponin / Q000187:drug effects / Q000378:metabolism*; D019209:Troponin C
D014336:Troponin; D019209:Troponin C; D002110:Caffeine; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D000205:Actomyosin; D017301:Ca(2+) Mg(2+)-ATPase; D009218:Myosins; D000252:Calcium-Transporting ATPases; D002122:Calcium Chloride; D002118:Calcium