Effects of 2,3-butanedione monoxime on cross-bridge kinetics in rat cardiac muscle.

The effects of 2,3-butanedione monoxime (BDM) on isometric force and myofibrillar adenosine 5'-triphosphatase (ATPase) activity were studied in skinned cardiac trabeculae from the rat. ATP hydrolysis was enzymatically coupled to the breakdown of reduced nicotinamide adeninedinucleotide (NADH). The NADH concentration was monitored photometrically. Measurements were performed at a sarcomere length of 2.1 microm, 20 degrees C and pH 7.0. Without BDM, isometric force was 45 +/- 3 kN/m2 and the isometric ATPase activity 0.49 +/- 0.04 mM/s (mean +/- SEM, n = 31). Force gradually decreased as a function of [BDM] to 2.8 +/- 0.4% at 100 mM BDM. ATPase activity was also depressed by BDM, but to a lesser extent than force. BDM therefore has a marked effect on myofibrillar tension cost. The rate of tension redevelopment after unloaded shortening decreased from 29 +/- 2 s-1 (n = 10) without BDM to 22 +/- 1 s-1 (n = 5) at 20 mM BDM. These results, modelled in a two- and three-state scheme of cross-bridge interaction, indicate that, in cardiac muscle, BDM not only affects cross-bridge formation but, especially at high concentrations (>/= 20 mM), also causes a marked increase in the apparent rate of cross-bridge detachment.