Effects of MgATP on ATP utilization and force under normal and simulated ischaemic conditions in rat cardiac trabeculae.
The dependency of ATP utilization and isometric force on [MgATP] was studied in skinned rat trabeculae under normal (pH 7.0) and simulated ischaemic (pH 6.2, 30 mM added Pi) conditions at 20+/-1 degrees C. At saturating [Ca2+], mean (+/-SEM) ATP utilization at 5 mM MgATP (A0) was 0.48+/-0.03 mM/s and force (F0) was 37+/-2 kN/m2. At 10 microM MgATP under normal conditions ATP utilization decreased gradually to 66+/-3% of A0, and force increased to 169+/-7% of F0. Under ischaemic conditions at 10 microM MgATP, ATP utilization decreased from 30+/-5% to 11+/-2% of A0 whereas force increased eightfold from 12+/-4% to 97+/-7% of F0. The [MgATP] at half-maximal ATP utilization (Km) under ischaemic conditions was 21+/-3 microM. At pH 7.0, Km was estimated to be less than 10 microM. These results show that tension cost decreases markedly with decreasing MgATP. Under ischaemic conditions parallel changes in Ca2+ sensitivity of force and ATP utilization were observed, corresponding to 1.3 pCa units. Reducing [MgATP] from 0.5 to 0.05 mM caused a modest reversal of this change in Ca2+ sensitivity. These changes in Ca2+ sensitivity are consistent with a marked reduction in active force and force-related ATP utilization during ischaemia but are insufficient to explain the ischaemic contracture on the basis of active force development.
Ebus
J P
JP
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Papp
Z
Z
Zaremba
R
R
Stienen
G J
GJ
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism*; D009243:NAD / Q000032:analysis; D051381:Rats
D009243:NAD; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D002118:Calcium